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Li-Ming Tian,1 Dan Ke2 1Department of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400000, People’s Republic of ChinaCorrespondence: Li-Ming TianDepartment of Dermatology, Wuhan No.1 Hospital, Hospital of Traditional Chinese and Western Medicine Affiliated to Hubei University of Chinese Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine Affiliated to Huazhong University of Science and Technology, No. 215 of Zhongshan Avenue, Qiaokou District, Wuhan, 430022, People’s Republic of ChinaTel +86 27 8533 2606Fax +86 27 8583 2563Email tianlm632587@tom.comDan KeDepartment of Dermatology, Chongqing Traditional Chinese Medicine Hospital, No. 40 of Daomenkou, Yuzhong District, Chongqing, 400000, People’s Republic of ChinaTel +86 23 6390 1120Fax +86 23 6373 1325Email ked98527@163.comObjective: To study the relationship between the single nucleotide polymorphisms (SNPs) of the human β-defensin 1-gene (DEFB1) and the genetic susceptibility of acne vulgaris in the Han Chinese ethnic group.Methods: A total of 104 patients with acne vulgaris and 126 healthy participants were included in our study. We analyzed the association between acne vulgaris and the polymorphisms in the DEFB1 G-52A, C-44G, and G-20A gene. We then analyzed the relationship between the different genotypes and the susceptibility to acne vulgaris.Results: The frequency of DEFB1 C-44G genetic polymorphisms between the acne vulgaris group and the control group was significantly different (P < 0.05). The frequency of DEFB1 G-20A genetic polymorphisms between the acne vulgaris group and the control group was also significantly different (P < 0.05).Conclusion: The − 44G or − 20A allele showed a low expression in acne vulgaris, which has already been shown to correlate with the low risk of acne vulgaris among Chinese Han patients. This further supports the contribution of the DEFB1 gene to the pathogenesis of acne.Keywords: human β-defensin 1, genetic polymorphisms, acne vulgaris, Cutibacterium acnes, Han Chinese

Background In recent decades, considerable attention has been paid to exploring the population genetic characteristics of Han Chinese, mainly documenting a north-south genetic substructure. However, the central Han Chinese have been largely underrepresented in previous studies. Aim To infer a comprehensive understanding of the homogenisation process and population history of Han Chinese. Subjects and methods We collected samples from 122 Han Chinese from seven counties of Hubei province in central China and genotyped 534,000 genome-wide SNPs. We compared Hubei Han with both ancient and present-day Eurasian populations using Principal Component Analysis, ADMIXTURE, f statistics, qpWave and qpAdm. Results We observed Hubei Han Chinese are at a genetically intermediate position on the north-south Han Chinese cline. We have not detected any significant genetic substructure in the studied groups from seven different counties. Hubei Han show significant evidence of genetic admixture deriving about 63% of ancestry from Tai-Kadai or Austronesian-speaking southern indigenous groups and 37% from Tungusic or Mongolic related northern populations. Conclusions The formation of Han Chinese has involved extensive admixture with Tai-Kadai or Austronesian-speaking populations in the south and Tungusic or Mongolic speaking populations in the north. The convenient transportation and central location of Hubei make it the key region for the homogenisation of Han Chinese.

ObjectivesMethamphetamine (METH) is a central nervous psychostimulant and one of the most frequently used illicit drugs. Numerous genetic loci that influence complex traits, including alcohol abuse, have been discovered; however, genetic analyses for METH dependence remain limited. An increased histone deacetylase 3 (HDAC3) expression has been detected in Fos-positive neurons in the dorsomedial striatum following withdrawal after METH self-administration. Herein, we aimed to systematically investigate the contribution of HDAC3 to the vulnerability to METH dependence in a Han Chinese population.MethodsIn total, we recruited 1,221 patients with METH dependence and 2,328 age- and gender-matched controls. For genotyping, we selected 14 single nucleotide polymorphisms (SNPs) located within ± 3 kb regions of HDAC3. The associations between genotyped genetic polymorphisms and the vulnerability to METH dependence were examined by single marker- and haplotype-based methods using PLINK. The effects of expression quantitative trait loci (eQTLs) on targeted gene expressions were investigated using the Genotype-Tissue Expression (GTEx) database.ResultsThe SNP rs14251 was identified as a significant association signal (χ2 = 9.84, P = 0.0017). An increased risk of METH dependence was associated with the A allele (minor allele) of rs14251 [odds ratio (95% CI) = 1.25 (1.09–1.43)]. The results of in silico analyses suggested that SNP rs14251 could be a potential eQTL signal for FCHSD1, PCDHGB6, and RELL2, but not for HDAC3, in various human tissues.ConclusionWe demonstrated that genetic polymorphism rs14251 located at 5q31.3 was significantly associated with the vulnerability to METH dependence in Han Chinese population.

In this study, Japanese and Han Chinese individuals (n = 32, each) were genotyped for 261 autosomal STRs, and allele frequencies were calculated for each locus in each population. The average number of alleles for all loci in Japanese and Han Chinese populations was 6.65 and 6.56, respectively. The tests for deviations from HWE performed using an exact test showed that the number of STRs (P > 0.05) in Japanese and Han Chinese populations was 236 and 241, respectively. Calculation of forensic parameters showed heterozygosity, and the exclusion means in the Japanese population were 0.7185 and 4813 and those in the Han Chinese population were 0.7308 and 0.5008. In addition, population genetic analyses, such as principal component analysis and factorial correspondence analysis, were performed and a differential formula with likelihood ratios was applied for various number of STR loci based on the effectiveness of differentiation between the two populations. Accordingly, this study suggests that statistical differentiation between genetically close populations, such as the Japanese and Han Chinese populations, is possible if approximately 40–50 effective STR loci are analyzed. [ABSTRACT FROM AUTHOR]

Background: High altitude pulmonary edema (HAPE) is a hypoxia-induced non-cardiogenic pulmonary edema that typically occurred in un-acclimatized lowlanders, which inevitably leads to life-threatening consequences. Apart from multiple factors involved, the genetic factors also play an important role in the pathogenesis of HAPE. So far, researchers have put more energy into the nuclear genome and HAPE, and ignored the relationship between the mitochondrion DNA (mtDNA) variants and HAPE susceptibility.Methods: We recruited a total of 366 individuals including 181 HAPE patients and 185 non-HAPE populations through two times. The first time, 49 HAPE patients and 58 non-HAPE individuals were performed through whole mtDNA sequences to search the mutations and haplogroups. The second time, 132 HAPE patients and 127 non-HAPE subjects were collected to apply verifying these mutations and haplogroups of mtDNA with the routine PCR method.Results: We analyzed and summarized the clinical characteristics and sequence data for the 49 HAPE patients and 58 non-HAPE individuals. We found that a series of routine blood indexes including systolic arterial blood pressure (SBP), heart rate (HR), white blood cell (WBC), and C-reactive protein (CRP) in the HAPE group presented higher and displayed significant differences compared with those in the non-HAPE group. Although the average numbers of variants in different region and group samples were not statistically significant (P > 0.05), the mutation densities of different regions in the internal group showed significant differences. Then we found two mutations (T16172C and T16519C) associated with the HAPE susceptibility, the T16172C mutation increased the risk of HAPE, and the T16519C mutation decreased the HAPE rating. Furthermore, the two mutations were demonstrated with 132 HAPE patients and 127 non-HAPE individuals. Unfortunately, all the haplogroups were not associated with the HAPE haplogroups.Conclusions: We provided evidence of differences in mtDNA polymorphism frequencies between HAPE and non-HAPE Han Chinese. Genotypes of mtDNA 16172C and 16519C were correlated with HAPE susceptibility, indicating the role of the mitochondrial genome in the pathogenesis of HAPE. [ABSTRACT FROM AUTHOR]

Objectives: Endometriosis is a common gynecological disease affecting up to ~10% of women at reproductive age. Prior combined studies implied that MARVELD2 might be involved in the pathogenesis of certain malignancies. Here, 211 Han Chinese samples with ovarian endometriosis were analyzed for the presence of MARVELD2 mutations. Methods: We analyze the potential presence of MARVELD2 mutations by direct DNA sequencing. Results: A total of 7 variants, 5 missense and 2 synonymous variants, were identified in our 211 ovarian endometriosis samples with different frequencies. Among the 5 missense variant, a missense rare variant p.V198M (c.592G>A), was identified in 10 out of our 211 samples (4.74%). This rare variant was identified with extremely low frequency in 766 control samples from 766 Chinese women without endometriosis (0.13%, 1/766) and control samples in the public databases. The evolutionary conservation analysis results suggested that the MARVELD2 rare variant lead to highly conserved amino acid substitutions among 14 vertebrate species from Human to Snake. Furthermore, both the SIFT and Polyphen-2 programs predicted this rare variant to be 'disease causing'. However, we failed to observe any statistical significance between the MARVELD2 rare variant and the available clinical data. Conclusions: We identified a potential pathogenic rare variant in the MARVELD2 gene in Chinese samples with ovarian endometriosis, indicating the MARVELD2 rare variant might play an active role in the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Background: Previous studies found that Asians seemed to have higher risk of HT after thrombolysis than Caucasians due to its race differences in genetic polymorphism. Whether the model developed by Caucasians could predict risk of symptomatic intracerebral hemorrhage (sICH) in Asians was unknown. Objectives: To develop a machine learning–based model for predicting sICH after stroke thrombolysis in Caucasians and externally validate it in an independent Han Chinese cohort. Design: The derivation Caucasian sample included 1738 ischemic stroke (IS) patients from the Virtual International Stroke Trials Archive (VISTA) data set, and the external validation Han Chinese cohort included 296 IS patients who were treated with intravenous thrombolysis. Methods: Twenty-eight variables were collected across both samples. According to their properties, we classified them into six distinct clusters (ie, demographic variables, medical history, previous medication, baseline blood biomarkers, neuroimaging markers on initial CT scan and clinical characteristics). A support vector machine (SVM) model, which consisted of data processing, model training, testing and a 10-fold cross-validation, was developed to predict the risk of sICH after stroke thrombolysis. The receiving operating characteristic (ROC) was used to assess the prediction performance of the SVM model. A domain contribution analysis was then performed to test which cluster had the highest influence on the performance of the model. Results: In total, 85 (4.9%) patients developed sICH in the Caucasians, and 29 (9.8%) patients developed sICH in the Han Chinese cohort. Eight features including age, NIHSS score, SBP (systolic blood pressure), DBP (diastolic blood pressure), ALP (alkaline phosphatase), ALT (alanine transaminase), glucose, and creatine level were included in the final model, all of which were from demographic, clinical characteristics, and blood biomarkers clusters, respectively. The SVM model showed a good predictive performance in both Caucasians (AUC = 0.87) and Han Chinese patients (AUC = 0.74). Domain contribution analysis showed that inclusion/exclusion of clinical characteristic cluster (NIHSS score, SBP, and DBP), had the highest influence on the performance of predicting sICH in both Caucasian and Han Chinese cohorts. Conclusion: The established SVM model is feasible for predicting the risk of sICH after thrombolysis quickly and efficiently in both Caucasian and Han Chinese cohort. [ABSTRACT FROM AUTHOR]

Abstract Background Knowledge of wild edible plants is an important part of traditional knowledge. It is closely related to traditional human agriculture, as well as biodiversity. This study aimed to conduct a detailed investigation and evaluation of wild edible plants that are collected and consumed by the Mongolian and Han locals in Daqinggou and to provide valuable data for the development and utilization of plant resources. Methods In the 9 site visits to the area of Daqinggou during the period of 2017–2019, the authors used key informant interviews, semistructured interviews, and questionnaires to collect utilization information regarding precollected species of local wild edible plants. By combining the data obtained from 101 key informants, the authors used the Cultural Food Significance Index (CFSI), a quantitative index to evaluate the relative importance of the wild edible plants that were discussed in the aforementioned interviews. Results The investigation results show that the Mongolian people provided 67 folk names, corresponding to 57 wild plants, and the Han Chinese provided 58 folk names, corresponding to 49 wild plants. A total of 61 edible wild plant species belonging to 29 families and 52 genera were recorded as edible resources for the locals in Daqinggou. The uses include grains, oil and fat resources, vegetables, fruits, beverages, condiments, and snacks. The most commonly reported purpose of wild edible plants is using them as vegetables, followed by using them as beverages and fruits. The most widely used edible parts are fruits, leaves, and other aerial parts. Eating raw and cooked plants are the usual methods of consuming wild edible plants according to the locals. In addition, the CFSI of 61 wild edible plant species shows that 27 species have characteristics of medical food. Conclusions The knowledge and experience of naming and consuming wild plants by the Mongolian people and Han Chinese in Daqinggou are an important manifestation of the direct interaction between locals and plants. The CSFI evaluation of the wild edible plants consumed by the locals in Daqinggou establishes the utilization of some wild plants as part of the traditional knowledge of medical food.

Background: Due to their long history, complex admixture processes and large population sizes, more research is required to explore the fine genetic structure of Han populations from different geographic locations of China. Aim: To characterise the paternal genetic structure of the Han Chinese in Henan province, which was once the central living region of the ancient Huaxia population, the precursors of the Han Chinese. Subjects and methods: We sequenced Y chromosomes of 60 males from Zhengzhou, Henan Province, and reconstructed a phylogenetic tree for these samples with age estimation. Results: We observed high diversity of paternal lineages in our collection. We found that the in situ Neolithic expansion of the “Major lineages” contributed to a large portion of the paternal gene pool of the Han population in Henan Province. We also detected a large number of “Minor lineages” that diverged in the Palaeolithic Age. Conclusion: We suggest that the high genetic diversity in the paternal gene pool of modern Han populations is mainly attributed to the reservation of a larger number of lineages that diverged in the Palaeolithic Age, while the recent expansion of limited lineages contributed to the majority of the gene pool of modern Han populations. We propose that such a structure is a basal characteristic for the genetic structure of modern Han populations.

Abstract Introduction Azathioprine is a synthetic purine analogue derived from 6-mercaptopurine which acts by disrupting nucleic acid synthesis and interfering with T cell activation. It is effective in dermatology diseases related to the immune system. However, its side effects, including severe neutropenia, kept patients from using it. Mutations in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA) genes account for the major genetic polymorphism markers for azathioprine adverse risk factors in Caucasians, but not in Asians. The predictive value of the nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) has been studied in various diseases among different populations. The aim of our study was to determine the contribution of NUDT15 mutations in azathioprine-induced neutropenia in Han Chinese patients with dermatologic diseases. Methods The study enrolled all consecutive patients, older than 13 years old, with dermatological diseases currently treated orally with azathioprine in our clinic. Samples were also collected from patients with documented leukopenia in our prior study that examined the association between TPMT, ITPA, and neutropenia after informed reconsent. Complete blood count, differential count, and hepatic and renal function were checked regularly. The DNA samples for NUDT15 genotype were obtained from the patients. Results In total, we enrolled 56 patients (39 male, 17 female). The NUDT15 genotypes are mostly C/C (N = 36, 64.29%). Heterozygous variant (C/T) accounts for 30.36% (N = 17) and homozygous variant (T/T) accounts for 5.36% (N = 3). Among these patients, 15 patients (26.79%) developed neutropenia, including all three patients carry homozygous variant (T/T). The age-, sex-, and dose-adjusted risk of heterozygous variant compared to wild type is 9.383 (95% CI 1.32–66.96). Conclusions Pretreatment screening of NUDT15 might reduce the chance of azathioprine-induced neutropenia in Han Chinese patients with dermatologic diseases.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger’s hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10−7–7.31 × 10−6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10−7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10−6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D’ = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

Background: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. Methods: A population-based case–control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. Results: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428–0.814, P = 0.001; and OR = 0.654, 95% CI 0.457–0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179–4.608, P = 0.015; OR = 2.033, 95% CI 1.242–3.322, P = 0.005; OR = 3.040, 95% CI 1.522–6.061, P = 0.002; and OR = 2.890, 95% CI 1.199–6.993, P = 0.018, respectively). Conclusions: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case–control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19. [ABSTRACT FROM AUTHOR]

The evolutionary and admixture history of Han Chinese have been widely discussed via traditional autosomal and uniparental genetic markers [e.g., short tandem repeats, low-density single nucleotide polymorphisms). However, their fine-scale genetic landscapes (admixture scenarios and natural selection signatures) based on the high-density allele/haplotype sharing patterns have not been deeply characterized. Here, we collected and generated genome-wide data of 50 Han Chinese individuals from four populations in Guizhou Province, one of the most ethnolinguistically diverse regions, and merged it with over 3,000 publicly available modern and ancient Eurasians to describe the genetic origin and population admixture history of Guizhou Hans and their neighbors. PCA and ADMIXTURE results showed that the studied four populations were homogeneous and grouped closely to central East Asians. Genetic homogeneity within Guizhou populations was further confirmed via the observed strong genetic affinity with inland Hmong-Mien people through the observed genetic clade in Fst and outgroup f3/f4-statistics. qpGraph-based phylogenies and f4-based demographic models illuminated that Guizhou Hans were well fitted via the admixture of ancient Yellow River Millet farmers related to Lajia people and southern Yangtze River farmers related to Hanben people. Further ChromoPainter-based chromosome painting profiles and GLOBETROTTER-based admixture signatures confirmed the two best source matches for southwestern Hans, respectively, from northern Shaanxi Hans and southern indigenes with variable mixture proportions in the historical period. Further three-way admixture models revealed larger genetic contributions from coastal southern East Asians into Guizhou Hans compared with the proposed inland ancient source from mainland Southeast Asia. We also identified candidate loci (e.g., MTUS2, NOTCH4, EDAR, ADH1B, and ABCG2) with strong natural selection signatures in Guizhou Hans via iHS, nSL, and ihh, which were associated with the susceptibility of the multiple complex diseases, morphology formation, alcohol and lipid metabolism. Generally, we provided a case and ideal strategy to reconstruct the detailed demographic evolutionary history of Guizhou Hans, which provided new insights into the fine-scale genomic formation of one ethnolinguistically specific targeted population from the comprehensive perspectives of the shared unlinked alleles, linked haplotypes, and paternal and maternal lineages.

ObjectivesSchizophrenia (SZ) is a complex psychiatric disorder with high heritability, and genetic components are thought to be pivotal risk factors for this illness. The glutamate decarboxylase 1 gene (GAD1) was hypothesized to be a candidate risk locus for SZ given its crucial role in the GABAergic neurotransmission system, and previous studies have examined the associations of single nucleotide polymorphisms (SNPs) spanning the GAD1 gene with SZ. However, inconsistent results were obtained. We hence examined the associations between GAD1 SNPs and SZ in two independent case-control samples of Han Chinese ancestry.Materials and MethodsTwo Han Chinese SZ case-control samples, referred as the discovery sample and the replication sample, respectively, were recruited for the current study. The discovery sample comprised of 528 paranoid SZ cases (with age of first onset ≥ 18) and 528 healthy controls; the independent replication sample contained 1,256 early onset SZ cases (with age of first onset < 18) and 2,661 healthy controls. Logistic regression analysis was performed to examine the associations between GAD1 SNPs and SZ.ResultsTen SNPs covering GAD1 gene were analyzed in the discovery sample, and two SNPs showed nominal associations with SZ (rs2241165, P = 0.0181, OR = 1.261; rs2241164, P = 0.0225, OR = 1.219). SNP rs2241164 was also nominally significant in the independent replication sample (P = 0.0462, OR = 1.110), and the significance became stronger in a subsequent meta-analysis combining both discovery and replication samples (P = 0.00398, OR = 1.138). Nevertheless, such association could not survive multiple corrections, although the effect size of rs2241164 was comparable with other SZ risk loci identified in genome-wide association studies (GWAS) in Han Chinese population. We also examined the associations between GAD1 SNPs and SZ in published datasets of SZ GWAS in East Asians and Europeans, and no significant associations were observed.ConclusionWe observed weak associations between GAD1 SNPs and risk of SZ in Han Chinese populations. Further analyses in larger Han Chinese samples with more detailed phenotyping are necessary to elucidate the genetic correlation between GAD1 SNPs and SZ.

The evolutionary and admixture history of Han Chinese have been widely discussed via traditional autosomal and uniparental genetic markers [e.g., short tandem repeats, low-density single nucleotide polymorphisms). However, their fine-scale genetic landscapes (admixture scenarios and natural selection signatures) based on the high-density allele/haplotype sharing patterns have not been deeply characterized. Here, we collected and generated genome-wide data of 50 Han Chinese individuals from four populations in Guizhou Province, one of the most ethnolinguistically diverse regions, and merged it with over 3,000 publicly available modern and ancient Eurasians to describe the genetic origin and population admixture history of Guizhou Hans and their neighbors. PCA and ADMIXTURE results showed that the studied four populations were homogeneous and grouped closely to central East Asians. Genetic homogeneity within Guizhou populations was further confirmed via the observed strong genetic affinity with inland Hmong-Mien people through the observed genetic clade in Fst and outgroup f 3 /f 4-statistics. qpGraph-based phylogenies and f 4-based demographic models illuminated that Guizhou Hans were well fitted via the admixture of ancient Yellow River Millet farmers related to Lajia people and southern Yangtze River farmers related to Hanben people. Further ChromoPainter-based chromosome painting profiles and GLOBETROTTER-based admixture signatures confirmed the two best source matches for southwestern Hans, respectively, from northern Shaanxi Hans and southern indigenes with variable mixture proportions in the historical period. Further three-way admixture models revealed larger genetic contributions from coastal southern East Asians into Guizhou Hans compared with the proposed inland ancient source from mainland Southeast Asia. We also identified candidate loci (e.g., MTUS2, NOTCH4, EDAR, ADH1B, and ABCG2) with strong natural selection signatures in Guizhou Hans via iHS, nSL, and ihh, which were associated with the susceptibility of the multiple complex diseases, morphology formation, alcohol and lipid metabolism. Generally, we provided a case and ideal strategy to reconstruct the detailed demographic evolutionary history of Guizhou Hans, which provided new insights into the fine-scale genomic formation of one ethnolinguistically specific targeted population from the comprehensive perspectives of the shared unlinked alleles, linked haplotypes, and paternal and maternal lineages. [ABSTRACT FROM AUTHOR]

Background: Over 200 schizophrenia risk loci have been identified by genome-wide association studies (GWASs). However, the majority of risk loci were identified in populations of European ancestry (EUR), potentially missing important biological insights. It is important to perform 5 GWASs in non-European populations.Methods: To identify novel schizophrenia risk loci, we conducted a GWAS in Han Chinese population (3493 cases and 4709 controls). We then performed a large-scale meta-analysis (a total of 143,438 subjects) through combining our results with previous GWASs conducted in EAS and EUR. In addition, we also carried out comprehensive post-GWAS analysis, including heritability partitioning, enrichment of schizophrenia associations in tissues and cell types, trancscriptome-wide association study (TWAS), expression quantitative trait loci (eQTL) and differential expression analysis.Results: We identified two new schizophrenia risk loci, including associations in SHISA9 (rs7192086, P = 4.92 × 10-08) and PES1 (rs57016637, P = 2.33 × 10-11) in Han Chinese population. A fixed-effect meta-analysis (a total of 143,438 subjects) with summary statistics from EAS and EUR identifies 15 novel genome-wide significant risk loci. Heritability partitioning with linkage disequilibrium score regression (LDSC) reveals a significant enrichment of schizophrenia heritability in conserved genomic regions, promoters, and enhancers. Tissue and cell-type enrichment analyses show that schizophrenia associations are significantly enriched in human brain tissues and several types of neurons, including cerebellum neurons, telencephalon inhibitory, and excitatory neurons. Polygenic risk score profiling reveals that GWAS summary statistics from trans-ancestry meta-analysis (EAS + EUR) improves prediction performance in predicting the case/control status of our sample. Finally, transcriptome-wide association study (TWAS) identifies risk genes whose cis-regulated expression change may have a role in schizophrenia.Conclusions: Our study identifies 17 novel schizophrenia risk loci and highlights the importance and necessity of conducting genetic study in different populations. These findings not only provide new insights into genetic etiology of schizophrenia, but also facilitate to delineate the pathophysiology of schizophrenia and develop new therapeutic targets. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses. Methods: We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data. Results: Our meta-analysis identified 18 significant (p < 5 × 10−8) and independent SNPs for fasting glucose. Interestingly, all 18 SNPs were meQTLs. The MR analysis identified seven CpGs near the G6PC2 gene that mediated the effects of a significant SNP (rs2232326) in the gene on fasting glucose. The MR effects for two CpGs were replicated using summary data based on the European population, using an exonic SNP rs2232328 in G6PC2 as the instrument. Conclusions/interpretation: Our analysis results suggest that rs2232326 and rs2232328 in G6PC2 may affect DNA methylation at CpGs near the gene and that the methylation may have downstream effects on fasting glucose. Therefore, SNPs in G6PC2 and CpGs near G6PC2 may reside along the pathway that influences fasting glucose levels. This is the first study to report CpGs near G6PC2, an important gene for regulating insulin secretion, mediating the effects of GWAS-significant SNPs on fasting glucose. [ABSTRACT FROM AUTHOR]

Objectives: Schizophrenia (SZ) is a complex psychiatric disorder with high heritability, and genetic components are thought to be pivotal risk factors for this illness. The glutamate decarboxylase 1 gene (GAD1) was hypothesized to be a candidate risk locus for SZ given its crucial role in the GABAergic neurotransmission system, and previous studies have examined the associations of single nucleotide polymorphisms (SNPs) spanning the GAD1 gene with SZ. However, inconsistent results were obtained. We hence examined the associations between GAD1 SNPs and SZ in two independent case-control samples of Han Chinese ancestry. Materials and Methods: Two Han Chinese SZ case-control samples, referred as the discovery sample and the replication sample, respectively, were recruited for the current study. The discovery sample comprised of 528 paranoid SZ cases (with age of first onset ≥ 18) and 528 healthy controls; the independent replication sample contained 1,256 early onset SZ cases (with age of first onset < 18) and 2,661 healthy controls. Logistic regression analysis was performed to examine the associations between GAD1 SNPs and SZ. Results: Ten SNPs covering GAD1 gene were analyzed in the discovery sample, and two SNPs showed nominal associations with SZ (rs2241165, P = 0.0181, OR = 1.261; rs2241164, P = 0.0225, OR = 1.219). SNP rs2241164 was also nominally significant in the independent replication sample (P = 0.0462, OR = 1.110), and the significance became stronger in a subsequent meta-analysis combining both discovery and replication samples (P = 0.00398, OR = 1.138). Nevertheless, such association could not survive multiple corrections, although the effect size of rs2241164 was comparable with other SZ risk loci identified in genome-wide association studies (GWAS) in Han Chinese population. We also examined the associations between GAD1 SNPs and SZ in published datasets of SZ GWAS in East Asians and Europeans, and no significant associations were observed. Conclusion: We observed weak associations between GAD1 SNPs and risk of SZ in Han Chinese populations. Further analyses in larger Han Chinese samples with more detailed phenotyping are necessary to elucidate the genetic correlation between GAD1 SNPs and SZ. [ABSTRACT FROM AUTHOR]

Abstract Background The GC haplotype of the vitamin D binding protein (encoded by the GC gene) might be a risk factor to the vitamin D (VD) nutritional status for many populations, while evidences from the Chinese Han population are sparse. We test the association between vitamin D binding protein genotypes and VD status as well as the metabolic parameters of glucose and lipids in a Han Chinese population. Methods In a cross-sectional study conducted at a health examination centre (registered in ClinicalTrials.gov as QLS2013), 2641 adults were included and grouped according to their plasma 25-hydroxyvitamin D (25OHD) concentrations as VD deficient (VDD), insufficient (VDI), or sufficient (VDS). The rs7041 and rs4588 genotypes were analysed with a molecular beacon-based qPCR method using blood samples. Results Plasma 25OHD concentrations were lower in the GC2/2, rs7041T/T, and rs4588A/A genotypes than the GC1f/1s, rs7041G/T, and rs4588C/C genotypes (P 0.05). Conclusions In a Han Chinese population, the GC2 haplotype or more exactly rs4588A is a risk factor for low VD status but is not associated with glucose and lipid metabolic disorders, which are inversely correlated with the circulating 25OHD concentration in males. Trial registration The study was retrospectively registered in January 2018 as NCT03406234 in the ClinicalTrials.gov online system.

Objective: To explore the influence by not performing an oral glucose tolerance test (OGTT) in Han Chinese over 40 years. Design: Overall, 6682 participants were included in the prospective cohort study and were followed up for 3 years. Methods: Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG), FPG and 2h-PG (OGTT), and HbA1c testing using World Health Organization (WHO) or American Diabetes Association (ADA) criteria were employed for strategy analysis. Results: The prevalence of diabetes is 12.4% (95% CI: 11.6–13.3), while the prevalence of prediabetes is 34.1% (95% CI: 32.9–35.3) and 56.5% (95% CI: 55.2–57.8) using WHO and ADA criteria, respectively. 2h-PG determined more diabetes individuals than FPG and HbA1c. The testing cost per true positive case of OGTT is close to FPG and less than 2h-PG or HbA1c. FPG, 2h-PG and HbA1c strategies would increase costs from complications for false-positive (FP) or false-negative (FN) results compared with OGTT. Moreover, the least individuals identified as normal by OGTT at baseline developed (pre)diabetes, and the most prediabetes individuals identified by HbA1c or FPG using ADA criteria developed diabetes. Conclusions: The prevalence of isolated impaired glucose tolerance and isolated 2-h post-load diabetes were high, and the majority of individuals with (pre)diabetes were undetected in Chinese Han population. Not performing an OGTT results in underdiagnosis, inadequate developing risk assessment and probable cost increases of (pre)diabetes in Han Chinese over 40 years and great consideration should be given to OGTT in detecting (pre)diabetes in this population. Further population-based prospective cohort study of longer-term effects is necessary to investigate the risk assessment and cost of (pre)diabetes.

In recent decades, considerable attention has been paid to exploring the population genetic characteristics of Han Chinese, mainly documenting a north-south genetic substructure. However, the central Han Chinese have been largely underrepresented in previous studies. To infer a comprehensive understanding of the homogenisation process and population history of Han Chinese. We collected samples from 122 Han Chinese from seven counties of Hubei province in central China and genotyped 534,000 genome-wide SNPs. We compared Hubei Han with both ancient and present-day Eurasian populations using Principal Component Analysis, ADMIXTURE, f statistics, qpWave and qpAdm. We observed Hubei Han Chinese are at a genetically intermediate position on the north-south Han Chinese cline. We have not detected any significant genetic substructure in the studied groups from seven different counties. Hubei Han show significant evidence of genetic admixture deriving about 63% of ancestry from Tai-Kadai or Austronesian-speaking southern indigenous groups and 37% from Tungusic or Mongolic related northern populations. The formation of Han Chinese has involved extensive admixture with Tai-Kadai or Austronesian-speaking populations in the south and Tungusic or Mongolic speaking populations in the north. The convenient transportation and central location of Hubei make it the key region for the homogenisation of Han Chinese. [ABSTRACT FROM AUTHOR]

To investigate the associations of Single Nucleotide Polymorphisms (SNPs) in the SNTB1 gene with high myopia in a Han Chinese population. Based on previous studies, four SNPs from the SNTB1 gene were chosen for genotyping. This is a case-control genetic association study comprising 193 high myopia participants and 135 normal emmetropic controls from a Han Chinese population. Allelic frequencies of the SNPs and haplotypes were compared to assess the associations of the SNPs with high myopia and axial length (AL). The SNPs rs7839488 (effect allele: A; OR = 0.685), rs4395927 (effect allele: T; OR = 0.692), and rs6469937 (effect allele: A; OR = 0.683) displayed significant associations with high myopia initially (P =.044, 0.049, and 0.035, respectively), but did not withstand permutation testing (all Ppermutation>0.05). rs6469937 displayed associations with high myopia in the dominant model (AG+AA: OR = 0.609) against GG (reference). rs6469937 was also associated with AL in the dominant model (AG+AA: Beta = −0.58) against GG (reference). The haplotype analysis demonstrated ATGA as the protective haplotype against high myopia, which remained statistically significant in permutation testing (Ppermutation = 0.045). Our findings are suggestive that SNTB1 is associated with high myopia in a Han Chinese population. [ABSTRACT FROM AUTHOR]

Genetic and environmental factors play crucial roles in the development of esophageal cancer (EC) and contribute uniquely or cooperatively to human cancer susceptibility. Sichuan is located in the interior of southwestern China, and the northern part of Sichuan is one of the regions with a high occurrence of EC. However, the factors influencing the high incidence rate of EC in the Sichuan Han Chinese population and its corresponding genetic background and origins are still poorly understood. Here, we utilized genome-wide single nucleotide polymorphisms (SNPs) and Y-chromosome short tandem repeats (Y-STRs) to characterize the genetic structure, connection, and origin of cancer groups and general populations. We generated Y-STR-based haplotype data from 214 Sichuan individuals, including the Han Chinese EC population and a control group of Han Chinese individuals. Our results, obtained from Y-STR-based population statistical methods (analysis of molecular variance (AMOVA), principal component analysis (PCA), and phylogenetic analysis), demonstrated that there was a genetic substructure difference between the EC population in the high-incidence area of northern Sichuan Province and the control population. Additionally, there was a strong genetic relationship between the EC population in the northern Sichuan high-incidence area and those at high risk in both the Fujian and Chaoshan areas. In addition, we obtained high-density SNP data from saliva samples of 60 healthy Han Chinese individuals from three high-prevalence areas of EC in China: Sichuan Nanchong, Fujian Quanzhou, and Henan Xinxiang. As inferred from the allele frequency of SNPs and sharing patterns of haplotype segments, the evolutionary history and admixture events suggested that the Han population from Nanchong in northern Sichuan Province shared a close genetic relationship with the Han populations from Xinxiang in Henan Province and Quanzhou in Fujian Province, both of which are regions with a high prevalence of EC. Our study illuminated the genetic profile and connection of the Northern Sichuan Han population and enriched the genomic resources and features of the Han Chinese populations in China, especially for the Y-STR genetic data of the Han Chinese EC population. Populations living in different regions with high incidences of EC may share similar genetic backgrounds, which offers new insights for further exploring the genetic mechanisms underlying EC., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mengge Wang reports statistical analysis and writing assistance were provided by Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China. Guanglin He reports financial support was provided by Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Prostatic calculi (PCal) are commonly present with prostate disease; we aim to map the incidence and associated clinical risk factors of PCal in Han Chinese. We retrospectively selected men who sought a medical check-up in 2018. Basic clinical items, including age, weight, height, prostate specific antigen (PSA), uric acid (UA), fasting blood glucose (FBG), urinalysis results, and transabdominal prostate ultrasound, were recorded. Univariate and logistic regression analyses were performed to evaluate whether these factors were associated with the presence of PCal. We recorded the parameters of laboratory tests and clinical information from 14,427 men; men with PCal comprised 51.65% of the total group and 76.61% of the subgroup of benign prostate hyperplasia (BPH) patients. All the enrolled parameters showed meaningful differences, but the logistic regression analysis only indicated significant effects related to age (OR = 1.044, 95% CI = 1.040–1.047, and p <.001), body mass index (BMI) (OR = 1.035, 95% CI = 1.022–1.048, and p <.001), UA (OR = 0.999, 95% CI = 0.999–1.000, and p =.029), BPH (OR = 2.923, 95% CI = 2.678–3.191, and p <.001), and prostate cysts (OR = 0.609, 95% CI = 0.471–0.788, and p <.001). The odds ratio of the predicted combined model is 1.068. PCal was detected in 51.65% of men among healthy Han Chinese and in 76.61% of BPH patients. Age, BMI, UA, BPH, and prostate cysts were independent risk factors for the presence of PCal. [ABSTRACT FROM AUTHOR]

Mutations in polymerase gamma gene (POLG) are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it. Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity. Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG. Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance. Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a complex joint disorder characterized by sclerosis of subchondral bone. The knee is one of the most commonly affected joints. Given that the genetic mechanisms underlying knee OA remain elusive, our study aims were to first confirm the association of the TGFA gene alleles with the risk of knee OA and, second, to evaluate the relationship between peripheral TGFA concentrations and knee OA in an independent Han Chinese population. Materials and Methods: We performed a case-control study consisting of 392 knee OA patients and 808 unrelated healthy controls. Single-marker-based association analyses and haplotype-based analyses using 3 single nucleotide polymorphisms (SNPs) were performed to confirm the association of TGFA gene alleles with the risk of knee OA. Furthermore, we used enzyme-linked immunosorbent assay (ELISA) kits to detect the peripheral blood TGFA concentrations in patients and healthy controls and then evaluated the relationships between the TGFA alleles and genotypes with serum TGFA levels. Results: We replicated the genetic association of the rs2862851 T allele with the risk of knee OA (p = 1.68 × 10−4, OR = 1.41). Moreover, we observed that the peripheral TGFA concentrations were higher in knee OA patients than in healthy controls (p = 8.15 × 10−13). The peripheral TGFA concentrations were significantly different among the various rs2862851 genotypes for both cases (p = 4.16 × 10−16) and controls (p = 7.24 × 10−19). The individuals with the TT genotype in both cases and controls, had the highest peripheral TGFA concentrations. Moreover, with the increase in knee OA grade, peripheral TGFA concentration also increased (p = 1.36 × 10−72). Conclusion: Our study confirmed the association of the TGFA gene with the risk of knee OA and identified a positive correlation between peripheral TGFA levels and the severity of knee OA in the Han Chinese population, providing clues for understanding the etiology of knee OA. [ABSTRACT FROM AUTHOR]

Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. Thirteen single-nucleotide polymorphisms (SNPs) of the raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P < 5 x 10−8) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and sushi multiple domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1,329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5/ANKRD30A, two genes involved in cancer development, were identified and replicated. Within RFTN1, two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T, and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in the CSMD1 gene showing a significant association with smoking initiation. Further bioinformatics functional assessment suggested that RFTN1 may participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population.

Abstract Background Shaanxi province, located in the upper Yellow River, has been evidenced as the geographic origin of Chinese civilization, Sino‐Tibetan‐speaking language, and foxtail or broomcorn millet farmers via the linguistic phylogenetic spectrum, archeological documents, and genetic evidence. Nowadays, Han Chinese is the dominant population in this area. The formation process of modern Shaanxi Han population reconstructed via the ancient DNA is on the way, however, the patterns of genetic relationships of modern Shaanxi Han, allele frequency distributions of high mutated short tandem repeats (STRs) and corresponding forensic parameters are remained to be explored. Methods Here, we successfully genotyped 23 autosomal STRs in 630 unrelated Shaanxi male Han individuals using the recently updated Huaxia Platinum PCR amplification system. Forensic allele frequency and parameters of all autosomal STRs were assessed. And comprehensive population genetic structure was explored via various typical statistical technologies. Results Population genetic analysis based on the raw‐genotype dataset among 15,803 Eurasian individuals and frequency datasets among 56 populations generally illustrated that linguistic stratification is significantly associated with the genetic substructure of the East Asian population. Principal component analysis, multidimensional scaling plots and phylogenetic tree further demonstrated that Shaanxi Han has a close genetic relationship with geographically close Shanxi Han, and showed that Han Chinese is a homogeneous population during the historic and recent admixture from the STR variations. Except for Sinitic‐speaking populations, Shaanxi Han harbored more alleles sharing with Tibeto‐Burman‐speaking populations than with other reference populations. Focused on the allele frequency correlation and forensic parameters, all loci are in accordance with the minimum requirements of HWE and LD. The observed combined probability of discrimination of 8.2201E‐28 and the cumulative power of exclusion of 0.9999999995 in Shaanxi Han demonstrated that the studied STR loci are informative and polymorphic, and this system can be used as a powerful routine forensic tool in personal identification and parentage testing. Conclusion Both the geographical and linguistic divisions have shaped the genetic structure of modern East Asian. And more forensic reference data should be obtained for ethnically, culturally, geographically and linguistically different populations for better routine forensic practice and population genetic studies.

Abstract Background The aim of this study was to investigate potential associations between CYP2B6 c.516G>T polymorphism and the occurrence and prognosis of acute leukemias (AL) in the Han population of Northwest China. Methods The CYP2B6 gene polymorphism was analyzed by PCR‐RFLP and Sanger DNA sequencing in 126 patients with AL and 161 healthy controls. Results Compared with controls, there were significantly higher frequencies of GT and TT genotypes and T alleles in AL patients (p .05), while the frequencies in AL patients with partial remission and no remission were significantly higher. The CYP2B6 allele frequency in Han Chinese in Northwest China was significantly different to that reported in Han Chinese and other ethnic minorities in southern China, Uygur Chinese, Vietnamese, African, German, British, Spanish, Turkish, and Argentinian populations; however, there was no significant difference compared with allele frequencies reported in Tibetan and Mongolian Chinese, Japanese, Korean, and American populations. Conclusion Our findings show a strong correlation of the CYP2B6 c.516G>T polymorphism in the Han population of Northwest China with AL, especially fusion gene‐positive AL, and indicate a poor prognosis after the first course of chemotherapy. Our findings also implicate the T allele in AL susceptibility and indicate the existence of racial and geographical differences in allele frequencies of CYP2B6 c.516G>T polymorphism.

In this study, we examined the Chinese Han and Mongolian, two ethnic groups that belong to the same national and geographic regions but vary in their degrees of social interdependence and independence. We assumed that the Mongolian, who have traditionally been known as a herding community, exhibit a greater independent social orientation compared to the Han Chinese, who have traditionally been known as an agrarian community. Through three different studies we used the explicit measurement of self-construal, implicit cultural task of self – inflation and the practice of name-giving (i.e., baby names as a cultural product) to test our hypothesis. The obtained results revealed that compared to Han Chinese, Mongolian scored higher on independent – self subscale, had greater levels of self-symbolic inflation and were less likely to give common names to their babies. These findings suggest that Mongolians are more independent than Han Chinese. In view of that, the present study contributes to a better understanding of the complexity of Chinese culture in terms of interdependence and independence, and provides further support for historical sustenance theory.

This paper examines how the Buddhist revival, the Chan revival, and recent popularity of transnational meditation practices have facilitated Chinese women practicing Buddhist meditation in contemporary China. With the influence of the opening of China and growing transnational networks, there has been an increasing number of Han Chinese monastics and lay people practicing transnational meditation, such as samādhi, vipassanā and mindfulness, in the past two decades. Despite the restriction of accessing Chan halls at monasteries, some Chinese nuns and laywomen have traveled to learn meditation in different parts of China, and international meditation centers in Southeast Asia to study with yogis from all over the world. Surprisingly some returned female travelers have taken significant roles in organizing meditation retreats, and establishing meditation centers and meditation halls. Through examining some ethnographic cases of Chinese nuns and laywomen, this paper argues that the transnational meditation movement has an impact not only on gender equality, especially concerning Chinese women practicing meditation, but also on the development of contemporary Chinese Buddhism. The significant role of Chinese female meditators in promoting Buddhist meditation can reflect a trend of re-positioning the Chan School in contemporary China.

Abstract Background Stroke has a high fatality and disability rate, and is one of the main burdens to human health. It is thus very important to identify biomarkers for the development of effective approaches for the prevention and treatment of stroke. Connexin37 is an anti-inflammatory cytokine and is involved in chronic inflammation and atherosclerosis. Recent studies have found that CONNEXIN37 gene variations are associated with atherosclerosis diseases, such as coronary heart disease and stroke, but its association with stroke in distinct human populations remains to be determined. We report here the analysis of the association of the single nucleotide polymorphisms (SNPs) of CONNEXIN37 with ischemic stroke in Han Chinese population. Methods Two SNPs of CONNEXIN37 gene were analyzed in 385 ischemic stroke patients and 362 hypertension control patients using ligase detection reaction (LDR) method. Results Logistic regression analysis demonstrated that, AG and GG genotypes of SNP rs1764390 and CC genotype of rs1764391 of CONNEXIN37 were associated with an increased risk of ischemic stroke, and that G allele of rs1764390 is a risk factor for ischemic stroke. Further, we found that SNP rs1764390 and SNP rs1764391 in CONNEXIN37 were associated with ischemic stroke under additive/dominant model, and recessive/dominant model, respectively. Conclusion Our results indicate that CONNEXIN37 gene polymorphism is an ischemic stroke risk factor in Northern Han Chinese.

Abstract Background Han Chinese, Japanese and Korean, the three major ethnic groups of East Asia, share many similarities in appearance, language and culture etc., but their genetic relationships, divergence times and subsequent genetic exchanges have not been well studied. Results We conducted a genome-wide study and evaluated the population structure of 182 Han Chinese, 90 Japanese and 100 Korean individuals, together with the data of 630 individuals representing 8 populations wordwide. Our analyses revealed that Han Chinese, Japanese and Korean populations have distinct genetic makeup and can be well distinguished based on either the genome wide data or a panel of ancestry informative markers (AIMs). Their genetic structure corresponds well to their geographical distributions, indicating geographical isolation played a critical role in driving population differentiation in East Asia. The most recent common ancestor of the three populations was dated back to 3000 ~ 3600 years ago. Our analyses also revealed substantial admixture within the three populations which occurred subsequent to initial splits, and distinct gene introgression from surrounding populations, of which northern ancestral component is dominant. Conclusions These estimations and findings facilitate to understanding population history and mechanism of human genetic diversity in East Asia, and have implications for both evolutionary and medical studies.

Background/Objective: Deep vein thrombosis (DVT) was thought to be uncommon in Asians and routine thromboprophylaxis in the form of anticoagulation for surgical patients was considered to be unnecessary. The current study aims to provide a contemporary epidemiology of venous thromboembolism in a population-based scale. Methods: Information from January 1, 2010 to December 31, 2011 was retrieved from a centralized computer public healthcare database serving mainly an ethnic Han Chinese population of 7.1 million. The incidence, demographics, and hospital mortality rates of DVT and pulmonary embolism (PE) were obtained, and analyzed for different surgical categories. Results: The overall annual incidences of DVT, PE alone, and PE with DVT were 30.0 per 100,000 population, 8.7 per 100,000 population, and 3.0 per 100,000 population, respectively. Overall male to female ratio was 1:1.24. Venous thromboembolic disease was more common with increasing age in both sexes. Thirty days' mortality rates associated with DVT, PE alone, and PE with DVT were 9.0%, 17.4%, and 13.3% respectively. Among the patients who received 103,023 major and intermediate surgical procedures in the study period, the mean incidence of postoperative DVT, PE alone, and PE with DVT were only 0.20% (203.5 patients), 0.08% (85.5 patients), and 0.04% (40.5 patients) respectively. Conclusion: Compared with a similar study 10 years ago, there seemed to be a general increase in incidence of DVT and PE. This study showed that postoperative thromboembolic events were not uncommon, with DVT occurring in up to 0.2% of patients and PE in 0.12% of patients in this longitudinal survey.

Susceptibility to primary biliary cholangitis (PBC) is in part genetically determined. In our previous PBC genome-wide association study (GWAS) in 1118 Han Chinese PBC and 4036 controls, we noted that multiple SNPs in the runt-related transcription factor 3 (RUNX3) regions showed a nominally significant association. The tag SNP rs7529070 was genotyped using a TaqMan assay in a separately collected 1435 PBC and 3205 controls. A meta-analysis with a combined 2553 PBC and 7241 controls showed that rs7529070 is still nominally associated with PBC (p = 1.7 × 10–4, odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.28). Further analysis indicated that the risk allele of rs7529070 (G allele) is in complete linkage disequilibrium (LD) (r2 = 1) with the G allele of rs4648889, which is known to be associated with increased RUNX3 expression. Bioinformatic analysis with existing expression data showed that the expression of RUNX3 is significantly increased in PBC patients (p = 0.001) and the expression level is correlated with disease severity. Consistently, we also found significantly increased RUNX3 expression (p < 0.01) in the livers of dnTGFβRII mice (a PBC mouse model). This study suggests that the RUNX3 locus may associate with PBC in Han Chinese. [ABSTRACT FROM AUTHOR]

Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. Thirteen single-nucleotide polymorphisms (SNPs) of the raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P < 5 x 10−8) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and sushi multiple domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1,329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5 / ANKRD30A , two genes involved in cancer development, were identified and replicated. Within RFTN1 , two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T, and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in the CSMD1 gene showing a significant association with smoking initiation. Further bioinformatics functional assessment suggested that RFTN1 may participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Endometriosis is a common gynecological disease affecting up to 10% of women at reproductive age. Prior combined studies implied that MYH8 mutations might exist in endometriosis. Here, 152 Han Chinese samples with ovarian endometriosis were analyzed for the presence of MYH8 mutations. Two heterozygous missense mutations in the MYH8 gene, c.1441A > C (p.I481L) and c.4057G > A (p.E1353K), were identified in our samples. These mutations were neither found in public databases nor detected in our 485 Han Chinese control women without endometriosis. The p.I481L-mutated sample belonged to 34-year-old, who had slightly elevated serum CA 125 (42.09 U/mL); while the sample with p.E1353K mutation belonged to 25 years old, who had a markedly increased serum CA125 (89.86 U/mL). The evolutionary conservation analysis results suggested that these MYH8 mutations caused highly conserved amino acid substitutions among vertebrate species. Both the mutations were predicted to be 'disease causing' by MutationTaster and SIFT programs. In addition, no association was observed between MYH8 mutations and the available clinical data. In summary, the present study identified two novel potential pathogenic mutations in the MYH8 gene in samples with ovarian endometriosis for the first time, implying that MYH8 mutations might play a positive role in the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the contribution of DNA methylation at the phospholipase A2 group VII (PLA2G7) gene, to the risk of developing brain arteriovenous malformations (BAVMs) and intracranial aneurysms (IAs) in a Han Chinese population. Seventy patients with BAVMs or IAs and 26 control subjects were recruited to evaluate PLA2G7 methylation by bisulfite pyrosequencing. CpG3 methylation at the PLA2G7 was significantly higher in BAVM patients than in the control group (Chr6,46735560, p = 0.042). Gender subgroup analysis showed that PLA2G7 CpG4 (Chr6,46735574, p = 0.033) and mean methylation (p = 0.037) levels were significantly associated with BAVM in males. However, in females, PLA2G7 methylations were much lower in IAs than in controls [CpG2 (Chr6,46735558), p = 0.030] and BAVMs [CpG2, p = 0.001; CpG4, p = 0.007; CpG6 (Chr6, 46735579), p = 0.024; mean, p = 0.013]. In addition, mean methylation of the PLA2G7 significantly correlated with apoB levels in all individuals (r = 0.288, p = 0.006), and with apoE in BAVM patients (r = 0.259, p = 0.016). The receiver operating characteristic (ROC) curve showed that PLA2G7 CpG3 methylation might be a predictor of BAVM risk in Han Chinese (area under curve (AUC) = 0.76, p = 0.008). PLA2G7 DNA methylation was significantly associated with the risk of developing BAVMs in males or IAs in females. Future studies on the PLA2G7 mechanisms should be performed on the pathogenesis of these cerebrovascular disorders. [ABSTRACT FROM AUTHOR]

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. This study proposed to screen candidate PACG-associated variants in Chinese Han people. Whole exome sequencing was applied to five confirmed PACG patients and two primary angle closure suspect individuals within a PACG-enriched Chinese Han family. A series of bioinformatics analyses were implemented to obtain high-risk single nucleotide variant (SNV) loci for PACG, which were subsequently used for linkage analysis for identifying linkage genome regions. In addition, MassARRAY SNV genotyping was applied to high-risk PACG loci as well as those within linkage regions in another independent cohort including 251 PACG and 251 normal samples to further screen high-confidence SNVs. A total of 27 loci in 19 genes remained after linkage analysis. The 19 genes were significantly enriched in biological processes tightly related to PACG, including retinol metabolism and salmonella infection. Two nonsynonymous SNV loci, rs897804 in exon15 of HOOK2 and rs3745193 in exon7 of GTPBP3, were recognized with higher variant frequency in PACG samples than that in control samples after association analysis of MassARRAY SNV genotyping data. This study sheds new light on the understanding of PACG incidence among Chinese Han people. [ABSTRACT FROM AUTHOR]

The integration of farmers and nomads in northwestern China during the Han Dynasty (206 BCE ~ 220 CE) provides a crucial opportunity to reconstruct the material exchanges, formation and development of the Silk Road in antiquity. The subsistence strategy is arguably an effective proxy for the integration of various groups of people (e.g. farmers and nomads). In this paper, we have reported new stable isotope data from the Huangwan tombs dated to the Han dynasty in middle Gansu, which was the key juncture between the Han and Xiongnu empire, in order to fill the gap and further understand the substance strategies employed by the local people. According to the results of plant remains and stable isotopic data, millet farming, the typical agricultural activities for the Han Chinese in the Central Plains, was also the primary lifestyle for the Huangwan people in the mid Gansu. More importantly, this shows fundamentally remarkable difference from the agricultural practices in the Bronze Age Gansu Corridor, which were based on a variety of crops, including wheat, barley and millet. This major shift in the subsistence production at Huangwan can be correlated to a wider historical background in which the Han empire showed increasing political and military presence in the Gansu Corridor, indicating that local indigenous nomads followed the lifestyle of Han Chinese (e.g., millet farming), and/or the Han immigrates maintained millet farming. [ABSTRACT FROM AUTHOR]

In this study, we examined the Chinese Han and Mongolian, two ethnic groups that belong to the same national and geographic regions but vary in their degrees of social interdependence and independence. We assumed that the Mongolian, who have traditionally been known as a herding community, exhibit a greater independent social orientation compared to the Han Chinese, who have traditionally been known as an agrarian community. Through three different studies we used the explicit measurement of self-construal, implicit cultural task of self – inflation and the practice of name-giving (i.e., baby names as a cultural product) to test our hypothesis. The obtained results revealed that compared to Han Chinese, Mongolian scored higher on independent – self subscale, had greater levels of self-symbolic inflation and were less likely to give common names to their babies. These findings suggest that Mongolians are more independent than Han Chinese. In view of that, the present study contributes to a better understanding of the complexity of Chinese culture in terms of interdependence and independence, and provides further support for historical sustenance theory. [ABSTRACT FROM AUTHOR]

Background: Due to their long history, complex admixture processes and large population sizes, more research is required to explore the fine genetic structure of Han populations from different geographic locations of China. Aim: To characterise the paternal genetic structure of the Han Chinese in Henan province, which was once the central living region of the ancient Huaxia population, the precursors of the Han Chinese. Subjects and methods: We sequenced Y chromosomes of 60 males from Zhengzhou, Henan Province, and reconstructed a phylogenetic tree for these samples with age estimation. Results: We observed high diversity of paternal lineages in our collection. We found that the in situ Neolithic expansion of the "Major lineages" contributed to a large portion of the paternal gene pool of the Han population in Henan Province. We also detected a large number of "Minor lineages" that diverged in the Palaeolithic Age. Conclusion: We suggest that the high genetic diversity in the paternal gene pool of modern Han populations is mainly attributed to the reservation of a larger number of lineages that diverged in the Palaeolithic Age, while the recent expansion of limited lineages contributed to the majority of the gene pool of modern Han populations. We propose that such a structure is a basal characteristic for the genetic structure of modern Han populations. [ABSTRACT FROM AUTHOR]

Background: Shaanxi province, located in the upper Yellow River, has been evidenced as the geographic origin of Chinese civilization, Sino‐Tibetan‐speaking language, and foxtail or broomcorn millet farmers via the linguistic phylogenetic spectrum, archeological documents, and genetic evidence. Nowadays, Han Chinese is the dominant population in this area. The formation process of modern Shaanxi Han population reconstructed via the ancient DNA is on the way, however, the patterns of genetic relationships of modern Shaanxi Han, allele frequency distributions of high mutated short tandem repeats (STRs) and corresponding forensic parameters are remained to be explored. Methods: Here, we successfully genotyped 23 autosomal STRs in 630 unrelated Shaanxi male Han individuals using the recently updated Huaxia Platinum PCR amplification system. Forensic allele frequency and parameters of all autosomal STRs were assessed. And comprehensive population genetic structure was explored via various typical statistical technologies. Results: Population genetic analysis based on the raw‐genotype dataset among 15,803 Eurasian individuals and frequency datasets among 56 populations generally illustrated that linguistic stratification is significantly associated with the genetic substructure of the East Asian population. Principal component analysis, multidimensional scaling plots and phylogenetic tree further demonstrated that Shaanxi Han has a close genetic relationship with geographically close Shanxi Han, and showed that Han Chinese is a homogeneous population during the historic and recent admixture from the STR variations. Except for Sinitic‐speaking populations, Shaanxi Han harbored more alleles sharing with Tibeto‐Burman‐speaking populations than with other reference populations. Focused on the allele frequency correlation and forensic parameters, all loci are in accordance with the minimum requirements of HWE and LD. The observed combined probability of discrimination of 8.2201E‐28 and the cumulative power of exclusion of 0.9999999995 in Shaanxi Han demonstrated that the studied STR loci are informative and polymorphic, and this system can be used as a powerful routine forensic tool in personal identification and parentage testing. Conclusion: Both the geographical and linguistic divisions have shaped the genetic structure of modern East Asian. And more forensic reference data should be obtained for ethnically, culturally, geographically and linguistically different populations for better routine forensic practice and population genetic studies. Population genetic analysis based on the raw‐genotype dataset among 15,803 Eurasian individuals and frequency dataset among 56 populations generally illustrated that linguistic stratification is significantly associated with the East Asian population genetic substructure. Principal component analysis, multidimensional scaling plots, and phylogenetic tree further demonstrated that Shaaxi Han has a close genetic relationship with geographically close Shanxi Han, and showed that Han Chinese is a homogeneous population during the historic and recent admixture. Except for Sinitic‐speaking populations, Shaanxi Han harbored more alleles sharing with Tibeto‐Burman‐speaking populations than with other reference populations. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate potential associations between CYP2B6 c.516G>T polymorphism and the occurrence and prognosis of acute leukemias (AL) in the Han population of Northwest China. Methods: The CYP2B6 gene polymorphism was analyzed by PCR‐RFLP and Sanger DNA sequencing in 126 patients with AL and 161 healthy controls. Results: Compared with controls, there were significantly higher frequencies of GT and TT genotypes and T alleles in AL patients (p <.05), particularly in fusion gene‐positive AL patients. There was no significant difference in CYP2B6 polymorphic genotypes and T alleles between AL patients with complete remission after the first course of chemotherapy and controls (p >.05), while the frequencies in AL patients with partial remission and no remission were significantly higher. The CYP2B6 allele frequency in Han Chinese in Northwest China was significantly different to that reported in Han Chinese and other ethnic minorities in southern China, Uygur Chinese, Vietnamese, African, German, British, Spanish, Turkish, and Argentinian populations; however, there was no significant difference compared with allele frequencies reported in Tibetan and Mongolian Chinese, Japanese, Korean, and American populations. Conclusion: Our findings show a strong correlation of the CYP2B6 c.516G>T polymorphism in the Han population of Northwest China with AL, especially fusion gene‐positive AL, and indicate a poor prognosis after the first course of chemotherapy. Our findings also implicate the T allele in AL susceptibility and indicate the existence of racial and geographical differences in allele frequencies of CYP2B6 c.516G>T polymorphism. [ABSTRACT FROM AUTHOR]

Objective. To present a systematic evaluation of 47 non-MHC ankylosing spondylitis (AS) susceptibility loci that have been initially discovered through white genome-wide association studies in Han Chinese. Methods. Originally, 10,743 samples representing north and south Chinese in 4 datasets were obtained. After data quality control and imputation, metaanalysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNP) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages of AS-associated variants were compared. Functional annotations of AS-associated variants were conducted using HaploReg, RegulomeDB, and rVarBase databases. Results. We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (p = 6.30 x 10-10), rs10050860 (p = 4.09 x 10-5) and rs8070463 (p = 1.03 x 10-4). Potential susceptible SNP within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15), and rs62074054 (17q21). Epistatic interactions between 3 ERAP1 SNP (rs17401719, rs30187, and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect, while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than in whites. Further genomic annotation pinpointed 35 candidate functional SNP, especially in the 2p15, ERAP1, and NPEPPS-TBKBP1 regions. Conclusion. Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1, and NPEPPS-TBKBP1 regions may play a critical role in AS pathogenesis across diverse populations. [ABSTRACT FROM AUTHOR]

Introduction: Azathioprine is a synthetic purine analogue derived from 6-mercaptopurine which acts by disrupting nucleic acid synthesis and interfering with T cell activation. It is effective in dermatology diseases related to the immune system. However, its side effects, including severe neutropenia, kept patients from using it. Mutations in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA) genes account for the major genetic polymorphism markers for azathioprine adverse risk factors in Caucasians, but not in Asians. The predictive value of the nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) has been studied in various diseases among different populations. The aim of our study was to determine the contribution of NUDT15 mutations in azathioprine-induced neutropenia in Han Chinese patients with dermatologic diseases. Methods: The study enrolled all consecutive patients, older than 13 years old, with dermatological diseases currently treated orally with azathioprine in our clinic. Samples were also collected from patients with documented leukopenia in our prior study that examined the association between TPMT, ITPA, and neutropenia after informed reconsent. Complete blood count, differential count, and hepatic and renal function were checked regularly. The DNA samples for NUDT15 genotype were obtained from the patients. Results: In total, we enrolled 56 patients (39 male, 17 female). The NUDT15 genotypes are mostly C/C (N = 36, 64.29%). Heterozygous variant (C/T) accounts for 30.36% (N = 17) and homozygous variant (T/T) accounts for 5.36% (N = 3). Among these patients, 15 patients (26.79%) developed neutropenia, including all three patients carry homozygous variant (T/T). The age-, sex-, and dose-adjusted risk of heterozygous variant compared to wild type is 9.383 (95% CI 1.32–66.96). Conclusions: Pretreatment screening of NUDT15 might reduce the chance of azathioprine-induced neutropenia in Han Chinese patients with dermatologic diseases. [ABSTRACT FROM AUTHOR]

Metronidazole, a widely used drug for the treatment of infections with anaerobic and facultative anaerobic bacteria and protozoa, can frequently cause metronidazole‐induced cutaneous adverse reactions (McADRs). The aim of the present study was to investigate the association between human leucocyte antigen (HLA) alleles and McADRs in a Chinese Han population. The frequency of HLA‐B*24:02 carriers among the McADR patients was 73.3%, which was significantly higher than that of the population controls (32.16%, OR = 5.80, 95% CI = [1.80‐18.72], Pc = 0.004) and of the metronidazole‐tolerant patients (26.67%, OR = 7.56, 95% CI = [2.02‐28.35], Pc = 0.004). Molecular docking showed that metronidazole and one of its major metabolites had the potential to bind in the HLA groove and that there was a relatively stable binding state of the HLA‐B*24:02‐metronidazole/the metabolite complex. The CDR3 repertoires of both T cell receptor (TCR)Vα and Vβ of the patients showed a significantly skewed or an oligoclonal distribution. The TCRVβ CDR3 of the patients shared a similar motif, "CASSxxxxxxQxF." The current study demonstrated that both the HLA‐A*24:02 allele and TCR are involved in the pathogenesis of McADRs. [ABSTRACT FROM AUTHOR]

Background: To investigate the associations of Single Nucleotide Polymorphisms (SNPs) in the VIPR2 and ZMAT4 genes with high myopia in a Han Chinese population. Materials and Methods: In this case-control genetic association study comprising 193 high myopia participants and 135 normal emmetropic controls from a Han Chinese population, 15 SNPs from the VIPR2 and ZMAT4 genes were selected for genotyping based on previous studies. Allelic frequencies of the SNPs and haplotypes were compared for association with high myopia and axial length (AL). Results: RS885863 (G-reference/A-effect) and RS7829127 (A-reference/G-effect) were significantly associated with high myopia (OR = 1.832, P =.045; OR = 0.539, P =.023 respectively). The associations of RS885863 with high myopia were observed under the dominant (GA+AA: OR = 1.972, P <.05) and co-dominant models (Heterozygous GA: OR = 1.874; Homozygous AA: OR = 5.310; P <.05) against GG (reference). The mean AL of GG was 25.94 mm, compared with that in GA and AA of 26.64 mm and 27.48 mm respectively. The associations of RS7829127 with high myopia were observed under the dominant (AG+GG: OR = 0.512, P <.05) and co-dominant models (Heterozygous AG: OR = 0.524; Homozygous GG: OR = 0.307; P <.05) against AA (reference). The mean AL of AA was 26.35 mm, compared with that in AG and GG of 25.62 mm and 25.17 mm respectively. The importance of RS885863 and RS7829127 were also highlighted by their being the constituent SNPs in the haplotypes (ACGA, P =.002; and GA, P =.008 respectively) that were significantly associated with high myopia. Conclusions: Our findings agree that RS885863 from VIPR2 and RS7829127 from ZMAT4 are significantly associated with high myopia in a Han Chinese population. [ABSTRACT FROM AUTHOR]

Abstract Background Tissue factor pathway inhibitor (TFPI) is the main physiological inhibitor of TF-induced blood coagulation process, and may play essential roles in the pathogenesis of major adverse cardiac events. This study was designed to determine whether the variation of TFPI was related with coronary artery disease (CAD) in the Han Chinese populations. Methods A total of 1271 patients with coronary atherosclerosis and 1287 normal individuals from northern China were enrolled in the present study. Four tagging single-nucleotide polymorphisms (SNPs) (rs7586970, rs6434222, rs10153820 and rs8176528) from TFPI were selected and genotyped by direct sequencing. And the genotypes of the above SNPs were determined in all these participants. Results In the populations from Beijing and Harbin, no significant case-control differences in the frequencies of TFPI polymorphism (rs10153820 and rs8176528) were observed between CAD patients and controls. Meanwhile, two SNPs of TFPI (rs7586970 and rs6434222) were found to be associated with CAD in both groups. In stratified analyses based on gender, smoking, hypertension, diabetes mellitus and hyperlipidemia, we further determined that the investigated genetic variations of the TFPI genes seemed to be related with diabetes mellitus in CAD patients. Conclusions Genetic variations of the TFPI genes seem to be related with CAD, which likely cooperate with metabolic risk factor (diabetes mellitus) and play critical roles in the pathogenesis of coronary artery disease.