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The aim of this study was to experimentally investigate the process of chloride binding and its sulfate-induced release in cementitious materials. The cementitious materials were replaced with hardened cement paste particles (HCPs) with water-to-cement ratios (w/c) of 0.35 and 0.45. A long-term immersion experiment of HCPs in 0.1 M sodium chloride solution was performed to investigate its chloride-binding capacity, and then it was immersed in sodium sulfate solutions with concentrations of 0.1 and 0.5 M to explore the release of chloride binding induced by sulfates. Silver nitrate titration and quantitative X-ray diffraction (QXRD) were used to measure the concentration of free chlorides in the solutions and the content of bound chlorides in HCPs, respectively. The results show that there is a higher chloride-binding capacity in HCPs with a w/c ratio of 0.45 compared to 0.35, and the content of chemically bound chlorides is associated with the formation and decomposition of Friedel's and Kuzel's salts in HCPs. The presence of sulfates can easily result in the release of bound chlorides in Friedel's salt, but it cannot cause a complete release of bound chlorides in Kuzel's salt. Physically bound chlorides are more easily released by sulfates than chemically bound chlorides, and a high w/c ratio or sulfate concentration can increase the release rate of bound chlorides in HCPs.

Lithium-sulfur batteries have theoretical specific energy higher than state-of-the-art lithium-ion batteries. However, from a practical perspective, these batteries exhibit poor cycle life and low energy content owing to the polysulfides shuttling during cycling. To tackle these issues, researchers proposed the use of redox-inactive protective layers between the sulfur-containing cathode and lithium metal anode. However, these interlayers provide additional weight to the cell, thus, decreasing the practical specific energy. Here, we report the development and testing of redox-active interlayers consisting of sulfur-impregnated polar ordered mesoporous silica. Differently from redox-inactive interlayers, these redox-active interlayers enable the electrochemical reactivation of the soluble polysulfides, protect the lithium metal electrode from detrimental reactions via silica-polysulfide polar-polar interactions and increase the cell capacity. Indeed, when tested in a non-aqueous Li-S coin cell configuration, the use of the interlayer enables an initial discharge capacity of about 8.5 mAh cm -2 (for a total sulfur mass loading of 10 mg cm -2 ) and a discharge capacity retention of about 64 % after 700 cycles at 335 mA g -1 and 25 °C., (© 2022. UChicago Argonne, LLC, Operator of Argonne National Laboratory.)

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P meta  = 8.36 × 10 -8 , OR = 1.29; rs7259428, 19q12, ZNF536, P meta  = 7.58 × 10 -8 , OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, P meta  = 1.95 × 10 -8 ; rs2414487, 15q21.3, LOC145783, P meta  = 4.53 × 10 -9 ; rs2106525, 7q31.1, MDFIC, P meta  = 6.24 × 10 -9 ). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice., (© 2021. The Author(s).)

Background: The predictive value of hemoglobin A1c (HbA1c) levels in non-diabetic patients with myocardial infarction undergoing percutaneous coronary intervention (PCI) is still controversial. This study aimed to evaluate whether HbA1c levels were independently associated with adverse clinical outcomes in non-diabetic patients with coronary artery disease (CAD) who had undergone PCI by performing a meta-analysis of cohort studies., Methods: This meta-analysis included non-diabetic patients with CAD who had undergone PCI. A systematic search for publications listed in the PubMed, Embase, and Cochrane Library databases from commencement to December 2018 was conducted. Studies evaluating the adverse clinical outcomes according to abnormal HbA1c levels in non-diabetic patients diagnosed with CAD who had undergone PCI were eligible. The primary outcomes were long-term all-cause deaths and long-term major adverse cardiac events, and the secondary outcome was short-term all-cause deaths. The meta-analysis was conducted with RevMan 5.3 and Stata software 14.0. Odds ratios (ORs) were pooled using a random or fixed-effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary., Results: Six prospective cohort studies involving 10,721 patients met the inclusion criteria. From the pooled analysis, abnormal HbA1c levels were associated with increased risk for long-term all-cause death (OR 1.39, 95% confidence interval [CI] 1.16-1.68, P = 0.001, I = 45%). Sub-group analysis suggested that abnormal HbA1c levels between 6.0% and 6.5% predicted higher long-term major adverse cardiac event (including all-cause deaths, non-fatal myocardial infarction, target lesion revascularization, target vessel revascularization, recurrent acute myocardial infarction, heart failure requiring hospitalization, and stent thrombosis) risk (OR 2.05, 95% CI 1.46-2.87, P < 0.001, I = 0). Contrarily, elevated HbA1c levels were not associated with increased risk of short-term all-cause death (OR 1.16, 95% CI 0.88-1.54, P = 0.300, I = 0)., Conclusions: An abnormal HbA1c level is an independent risk factor for long-term adverse clinical events in non-diabetic patients with CAD after PCI. Strict control of HbA1c levels may improve patient survival. Further studies in different countries and prospective cohort studies with a large sample size are required to verify the association.

Background: Endothelial dysfunction may play a key role in non-obstructive coronary artery atherosclerosis. Our study aimed to evaluate the vascular endothelial function and its influencing factors in patients with non-obstructive coronary artery atherosclerosis., Methods: A total of 131 consecutive patients with non-obstructive coronary artery atherosclerosis were enrolled. Flow-mediated dilatation (FMD) was measured at baseline and 1-year follow-up. Endothelial progenitor cells (EPCs) were counted by staining the fasting venous blood with antibodies against CD34 and vascular endothelial growth factor receptor 2., Results: Systolic blood pressure, pulse pressure and the levels of HbA1c in participants with baseline FMD < 6% (n = 65) were significantly higher than those with baseline FMD ≥ 6% (n = 66). Baseline FMD was negatively associated with EPC counts (r = - 0.199, P < 0.05) and systolic blood pressure (r = - 0.315, P < 0.01). The 1-year FMD was significantly increased compared to the baseline FMD [(9.31 ± 5.62) % vs (7.31 ± 5.26) %, P < 0.001]. Independent predictors of FMD improvement included elevated EPC counts (OR = 1.104, 95% CI: 1.047-1.165, P < 0.001) and decreased levels of serum creatinine (OR = 0.915, 95% CI: 0.843-0.993, P = 0.034)., Conclusions: Family history of premature cardiovascular diseases, hypertension, elevated systolic pressure, and HbA1c > 6.5% are independent risk factors for endothelial dysfunction in non-obstructive atherosclerotic patients. Elevated peripheral blood EPC counts and decreased levels of serum creatinine are independent predictors of endothelial function improvement.

Exosome secretion is an important paracrine way of endothelial progenitor cells (EPCs) to modulate resident endothelial cells. The osteocalcin (OCN)-expressing EPCs have been found to be increased in cardiovascular disease patients and are considered to be involved in the process of coronary atherosclerosis. Since OCN has been proven to prevent endothelial dysfunction, this study aimed to evaluate the effect of exosomes derived from OCN-overexpressed EPCs on endothelial cells. Exosomes derived from EPCs (Exos) and OCN-overexpressed EPCs (OCN-Exos) were isolated and incubated with rat aorta endothelial cells (RAOECs) with or without the inhibition of OCN receptor G protein-coupled receptor family C group 6 member A (GPRC6A). The effects of exosomes on the proliferation activity of endothelial cells were evaluated by CCK-8 assay, and the migration of endothelial cells was detected by wound healing assay. A tube formation assay was used to test the influence of exosomes on the angiogenesis performance of endothelial cells. Here, we presented that OCN was packed into Exos and was able to be transferred to the RAOECs via exosome incorporation, which was increased in OCN-Exos groups. Compared with Exos, OCN-Exos had better efficiency in promoting RAOEC proliferation and migration and tube formation. The promoting effects were impeded after the inhibition of GPRC6A expression in RAOECs. These data suggest that exosomes from OCN-overexpressed EPCs have a beneficial regulating effect on endothelial cells, which involved enhanced OCN-GPRC6A signaling.

Background: The mortality of cardiovascular disease is constantly rising, and novel biomarkers help us predict residual risk. This study aimed to evaluate the predictive value of serum homocysteine (HCY) levels on prognosis in patients with ST-segment elevation myocardial infarction (STEMI)., Methods: The 419 consecutive patients with STEMI, treated at one medical center, from March 2010 to December 2015 were retrospectively investigated. Peripheral blood samples were obtained within 24 h of admission and HCY concentrations were measured using an enzymatic cycling assay. The patients were divided into high HCY level (H-HCY) and low HCY level (L-HCY) groups. Short- and long-term outcomes were compared, as were age-based subgroups (patients aged 60 years and younger vs. those older than 60 years). Statistical analyses were mainly conducted by Student t-test, Chi-squared test, logistic regression, and Cox proportional-hazards regression., Results: The H-HCY group had more males (84.6% vs. 75.4%, P = 0.018), and a lower prevalence of diabetes (20.2% vs. 35.5%, P < 0.001), compared with the L-HCY group. During hospitalization, there were seven mortalities in the L-HCY group and 10 in the H-HCY group (3.3% vs. 4.8%, P = 0.440). During the median follow-up period of 35.8 (26.9-46.1) months, 33 (16.2%) patients in the L-HCY group and 48 (24.2%) in the H-HCY group experienced major adverse cardiovascular and cerebrovascular events (MACCE) (P = 0.120). History of hypertension (hazard ratio [HR]: 1.881, 95% confidence interval [CI]: 1.178-3.005, P = 0.008) and higher Killip class (HR: 1.923, 95% CI: 1.419-2.607, P < 0.001), but not HCY levels (HR: 1.007, 95% CI: 0.987-1.027, P = 0.507), were significantly associated with long-term outcomes. However, the subgroup analysis indicated that in older patients, HCY levels were significantly associated with long-term outcomes (HR: 1.036, 95% CI: 1.011-1.062, P = 0.005)., Conclusion: Serum HCY levels did not independently predict in-hospital or long-term outcomes in patients with STEMI; however, among elderly patients with STEMI, this study revealed a risk profile for late outcomes that incorporated HCY level.

The study was aimed to investigate the protective effect and pharmacodynamic difference of the ethanol extracts of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus on the drug-induced liver injury induced by acetaminophen.The cell activations of LO2 cells treated by Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts were tested by CCK-8 essay.The effects of ethanol extracts on cell survival rate,the activities of ALT and AST in culture medium were detected based on the injury model of LO2 cells induced by APAP.Further,in purpose to observe the protective effect of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts on a mouse model of liver injury induced by intraperitoneal injectionof acetaminophen was established.Mice were randomly divided into control group,model group,positive drug group and Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts administration groups.The activities of ALT and AST in the serum and the levels of MDA,SOD,GSH and GSH-PX in the liver homogenate of the mice were detected by commercial kits.The HEstaining was used to observe the histopathological changes of liver tissue in each group and the TUNEL staining was used to observe the hepatocyte apoptosis.The results showed that the ethanol extracts at less than 1 g·L~(-1)did not affect the activity of LO2 cell.Compared with the model group,the cell survival rates of the Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups was significantly increased;the ALT and AST in the culture medium were distinct decreased(P<0.05 or P<0.01).The survival rate of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract from different batches were similar,while that of the Schisandrea Sphenatherae Fructus ethanol extract from different batches were quite different(P<0.05or P<0.01).Further,animal experiments showed that Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups could markedly inhibit the increase of ALT and AST levels in serum(P<0.01),decrease MDA content significantly(P<0.01),and increase GSH,GSH-PX and SOD activity significantly(P<0.01).Among them,compared with other groups,Schisandrae Sphenantherae Fructus ethanol extract-2 group showed the best effect(P<0.05 or P<0.01)while Schisandrae Sphenantherae Fructus ethanol extract-1 showed a poor effect(P<0.05 or P<0.01).In conclusion,both Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts have protective effect on APAP-induced drug-induced liver injury and there was a certain difference in the efficacy between Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts from different habitats.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607&#95;A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10 -19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607&#95;A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Large cohort-based genetic association studies have been established over a decade. However, for certain diseases, different results with respect to the genome-wide association study level have been obtained among studies, even for those conducted within the same ethnic groups. We hypothesized that onset age-based sample variables might have a great impact on the results., Methods: In the present study, we divided psoriasis patients into several subgroups according to the onset age bracket. We conducted genetic association analysis in the major histocompatibility complex (MHC) region of each patient subgroup with shared control subjects., Results: We found decreases in the numbers of susceptible variants in each subgroup analysis as the onset age increased in the longitudinal analysis. Meanwhile, the pairwise analysis showed that younger patients exhibited greater numbers of genetic risks in the MHC region compared to elder patients, regardless of whether the cut-off values were defined as 20 or 30 years old. Similar results were also found among 11-20-, 21-30- and 31-40-year-old groups. Furthermore, when combining the results of both the stepwise regression analysis and the HLA-C*06:02 conditioning analysis, different variants were found to be independently associated with each psoriasis subgroup., Conclusions: Onset age-based sample variables influence the results of genetic association studies, at least in MHC region-based genetic analysis. We suggest that caution is required when selecting samples for genetic association studies to prevent confounders that might be a result of onset age., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population., Objectives: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS)., Methods: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells., Results: Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls., Conclusions: This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE., (© 2017 British Association of Dermatologists.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. The 5q22.1 region was found to have an association with AD in our previous genome-wide association study (GWAS)., Objective: To identify the AD susceptibility gene in 5q22.1 and observe its expression in AD tissues., Methods: Suggestive indels from the GWAS data were genotyped in 3013 AD patients and 5075 controls from the Chinese Han population with the SequenomMassArray system. Association, Bayesian and bioinformatics analyses were used to identify possible causal indels and genes in the 5q22.1 region. Immunohistochemistry (IHC) was performed to observe protein expression in the tissues. PLINK 1.07 software was used for all statistical analyses., Results: The genotyping and association analysis showed that six deletions and four SNPs were associated with AD (P<0.005). The rs11357450 (P combined =7.79E-04, OR=1.39, logBayes Factor=1.29) deletion located in TMEM232 was identified to be the strongest variant. Analysis of the genetic model revealed that the dominant model best described rs11357450 (P=1.96E-03, OR=1.22; 95% CI=1.07-1.37). IHC showed that the expression of TMEM232 decreased gradually from the granular layer to the basal layer in AD, but in normal tissues, this trend was reversed. Additionally, positive cytoplasm staining was found in lymphocytes around the blood vessels in AD., Conclusions: The study indicates that TMEM232 in the 5q22.1 region is the causal gene for AD in the Chinese Han population., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2 , a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3 Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals., Competing Interests: The authors declare no conflict of interest.

Effects of sodium carboxymethyl cellulose (CMC) and hydroxypropyl methyl cellulose (HPMC) on the pasting, viscoelastic, and morphological properties of rice starch gel were studied. The addition of CMC increased the peak and trough viscosities, while decreased the final and setback viscosities of rice starch. The peak and trough viscosities of rice starch gel were only little affected by the addition of HPMC. The dynamic viscoelastic result showed that the addition of CMC significantly increased the values of storage modulus (G') and loss modulus (G″), while reduced the value of tanδ as compared to the control sample. Only a small increase in values of G' and G″ was observed in the case of HPMC. The rice starch gel with CMC addition exhibited higher resistances to the stress and produced a stronger gel network. The creep recovery data were well fitted by a four-element Burger's model. Furthermore, the morphological characteristics were in agreement with the finding of rheological results. It was concluded that the addition of CMC and HPMC modified the rheology of rice starch gel in different ways and interacted under different models based on their molecular structures., Practical Applications: Gluten-free foods such as rice cake are essential for people who suffer from celiac disease which is a digestive disorder caused by the consumption of grains containing gluten. The use of CMC and HPMC represents the most widespread approach used to mimic gluten in the manufacture of gluten-free breads based on rice starch, due to their structure-building and water-binding properties. Therefore, it is necessary and crucial to investigate the physical-chemical properties such as pasting and rheological properties of the rice starch with these hydrocolloids. In addition, a better understanding of the interactions of CMC and HPMC on the rice starch could provide additional tools for selection of gluten free recipes with improved rheological and textural properties., (© 2016 Wiley Periodicals, Inc.)

Dermatomyositis (DM) is a polygenic disorder characterized by inflammation of skeletal muscle and skin. To date, the exact etiopathogenesis of DM remains elusive. To explore the genetic basis of DM, we conducted genome-wide genotyping analysis of 127 patients and 1566 healthy controls by Illumina Human OmniZhongHua-8 BeadChips in the Chinese Han population. We investigated whether the three SNP (rs7750458, rs9501251 and rs9500928) at 6p21.32 in the HLA-DPB1 gene were significantly associated with DM (P < 5 × 10 -8 ) and identified two susceptibility loci at 7q34 (PIP, rs9986765, P = 7.45 × 10 -7 , odds ratio [OR] = 2.71) and 10q24.2 (CPN1, rs3750716, P = 9.04 × 10 -7 , OR = 4.39) with suggestive evidence. We imputed 6674 classical human leukocyte antigen (HLA) alleles, amino acids and SNP from the discovery dataset, and stepwise analysis revealed that HLA-DPB1*17 in class II HLA genes were significantly associated with DM susceptibility. This study represents the first genome-wide association study (GWAS) of DM in the Chinese Han population. For the first time, HLA-DPB1 was found to be associated with DM in this population. Moreover, we identified two novel suggestive susceptibility loci (PIP and CPN1) and confirmed four previously reported genes (DMB, DQA1, DQB1 and DRB1) having potential associations with DM in the Chinese Han population. Our GWAS results in this population should provide important information regarding the genetic etiopathogenesis of DM and facilitate the development of new therapies for the treatment of DM and the prevention of DM progression., (© 2016 Japanese Dermatological Association.)

Effects of sucrose fatty acid esters (SEs) with hydrophilic-lipophilic balance (HLB) values of 5 (S-570), 9 (S-970), and 15 (S-1570) on the pasting and rheological properties of waxy rice flour (WRF) were investigated. Rapid Visco Analyzer (RVA) showed that addition of SEs affected the pasting properties of WRF. Rheological experiment includes the steady shear flow characteristics, and dynamic viscoelastic properties were also determined using a controlled-stress rheometer. The steady shear tests demonstrated that the viscosity data fitted well with the power law model ( R 2 ≥0.976) and all WRF pastes exhibited typical pseudoplastic and shear-thinning properties. Dynamic rheological measurements revealed that the addition of S-970 and S-1570 significantly increased the values of G' and G″ of samples, whereas the addition of S-570 decreased these values. The addition of S-1570 reduced the value of tan δ , whereas S-570 and S-970 increased it.

Background: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations., Objective: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population., Methods: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform. Data were analyzed with PLINK 1.07 software., Results: We found that rs12634229 (3q13.2), rs7927894 (11p13.5) and rs878860 (11p15.4) showed a slight association with AD (P = 0.012, P = 0.033, P = 0.020, respectively); rs6780220 (3p21.33) was preferentially related to AD with keratosis pilaris, but did not reach the threshold of significance after correction. The frequency of rs7927894 allele T was significantly different between AD patients with a positive and negative family history of atopy., Conclusion: The loci rs7927894 (11p13.5) are related to AD with a positive family history of atopy in Chinese Han population, providing novel insight into the genetic pathogenesis of AD.

Rationale: IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene-gene interactions in the five genes among asthmatic children of Chinese Han nationality., Methods: Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor-dimensionality reduction method was applied for the analysis., Results: A four-way gene-gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E-05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E-03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E-03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E-03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E-03)., Conclusions: Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children., (© 2015 Wiley Periodicals, Inc.)

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

Unlabelled: Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], Pmeta =1.28 × 10(-34) ; and rs422951 [T320A] in NOTCH4, Pmeta  = 5.33 × 10(-16) ); one synonymous variant (rs378352 in HLA-DOA corresponding to HLA-DOA*010101, Pmeta  = 1.04 × 10(-23) ); and one noncoding variant (rs2853953 near HLA-C, Pmeta  = 5.06 × 10(-20) ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, Pmeta  = 2.95 × 10(-15) ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA-C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA-DQB1, rs7453920 at HLA-DQB2, rs3077 at HLA-DPA1, and rs9277535 at HLA-DPA2, which are all located in the HLA region, 9.84 × 10(-71)  ≤ Pmeta  ≤ 9.92 × 10(-7) )., Conclusion: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease., (© 2015 by the American Association for the Study of Liver Diseases.)

Introduction: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Currently, numerous genetic loci of SLE have been confirmed. Here we try to further explore additional genes contributing to SLE susceptibility in this study., Methods: Forty nine single nucleotide polymorphisms (SNPs) with moderate-risk for SLE in previous study were genotyped in a large-scale replication study with a total of 3,522 cases and 8,252 controls using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate through PLINK 1.07 software., Results: This replication effort confirmed five reported SLE susceptibility loci reaching genome-wide levels of significance (P(meta) <5.00 × 10(-08)): TNFSF4 (rs1418190, odds ratio (OR) = 0.81, P(meta) = 1.08 × 10(-08); rs4916219, OR = 0.80, P(meta )= 7.77 × 10(-09)), IRF8 (rs2934498, OR = 1.25, P(meta) = 4.97 × 10(-09)), miR-146a (rs2431697, OR = 0.69, P(meta) = 1.15 × 10(-22)), CD44 (rs2732547, OR = 0.82, P(meta) = 1.55 × 10(-11)), and TMEM39A (rs12494314, OR = 0.84, P(meta) = 1.01 × 10(-09)). Further logistic regression analysis indicated that the genetic effects within TNFSF4 detected in this study are independent from our previously reported signals., Conclusions: This study increases the number of established susceptibility loci for SLE in Han Chinese population and highlights the contribution of multiple variants of modest effect. Although further studies will be required to identify the causal alleles within these loci, the findings make a significant step forward in our understanding of the genetic contribution to SLE in Chinese population.

Increasing evidence indicates that polymorphisms in genes relevant to spermatogenesis might modulate the efficiency of reproduction in men. Ring finger protein 8 (RNF8) and bromodomain testis-specific (BRDT) are two candidate genes associated with spermatogenesis. Here, we considered potential associations of 14 single nucleotide polymorphisms (SNPs) in RNF8 and BRDT genes in Chinese patients with non-obstructive azoospermia (NOA). We analyzed 361 men with NOA and 368 fertile controls by using Sequenom iplex technology. Our data did not reveal any variants associated with NOA susceptibility. However, we observed that rs104669 and rs195432 of RNF8 were in strong linkage disequilibrium. Haplotype analysis of the two SNPs indicated that the haplotype AC reduced the risk of NOA and the haplotype TC significantly evaluated the risk of NOA. Moreover, the RNF8 variants rs195432 (C/A p = 0.030), rs195434 (T/C p = 0.025), and rs2284922 (T/C p = 0.034) were correlated with the smaller testis volume.

Purpose: To research the association between the single nucleotide polymorphisms (SNPs) of three spermatogenesis-related genes (USF1, GTF2A1L and OR2W3) and non-obstruction azoospermia (NOA)., Methods: We investigated 361 NOA cases and 368 controls from the Chinese Han population, and we used Sequenom iplex technology to analyze the candidate 9 SNPs from the USF1, GTF2A1L and OR2W3 genes., Results: In this study, we found that the variant rs2516838 of USF1 was associated with NOA susceptibility (P = 0.020, OR = 1.436), and the haplotype TCG of the variants rs1556259, rs2516838, and rs2774276 of USF1 conferred an increased risk of NOA (P = 0.019, OR = 1.436). Furthermore, we found that the rs11204546 genotype of OR2W3 and the rs11677854 genotype of GTF2A1L were correlated with the FSH level in the patients (P = 0.004 and P = 0.018, respectively)., Conclusions: Our results provided a new insight into susceptibility of USF1 variant with male infertility. Clinically, the SNPs (rs11204546 of OR2W3 and rs11677854 of GTF2A1L ) might be additional valuable molecular predictive markers for assessing the treatment of NOA patients.

Purpose: (1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor-cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer., Methods: We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC)., Results: We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk (P = 1.53 × 10(-4), odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511-0.808 and P = 1.59 × 10(-4), OR 0.642, 95 %CI 0.510-0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer (P = 0.042, OR 1.279, 95 % CI 1.008-1.622 and P = 0.047, OR 1.334, 95 % CI 1.003-1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking (P = 0.029, OR 0.343, 95 % CI 0.127-0.926 and P = 0.029, OR 0.343, 95 %CI 0.127-0.926) and OPN rs1126772 revealed associations with tumor-node-metastasis (TNM) stage (P = 0.025, OR 1.765, 95 % CI 1.073-2.905) and tumor differentiation (P = 0.031, OR 1.722, 95 % CI 1.049-2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion (P = 0.013), TNM stage (P = 0.003) and lymph node metastasis (P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size (P = 0.005) and lymph node metastasis (P = 0.023), respectively. The OPN expression displayed a positive association with CD44 (P = 0.01, r s = 0.164)., Conclusions: We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer.

Objective: The purpose of this study was to evaluate the relationship between body mass index (BMI) and a physical fitness index (PFI) in Chinese college freshmen based on 50-meter run., Design and Methods: Cross-sectional survey from 2007 to 2009. The records of 3825 men (age 18-31) and 4062 women (age 18-30) studying in Anhui medical university were examined. Height and weight were measured by trained teachers, and 50-meter run test was performed as PFI., Result: More men than women were overweight or obese (5.8% vs 2.1%), but more women than men were underweight (21.1% vs 16.9%). In all five BMI groups, men performed significantly better than women (p < 0.05). In both genders, decreasing performance was observed from normal weight or underweight to overweight and thinness (p for trend < 0.05). The relationship between BMI and PFI of men is nonlinear and varies with age, and the curvature of this parabola increases continuously. The relationship between BMI and PFI of women is not clear., Conclusion: The relationship between PFI and BMI of adult men conforms to the quadratic model, and the influence of PFI by BMI is more serious in middle-age male than youth male.

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.

To determine whether recent genome-wide association studies that reported 45 susceptibility loci in European women are also risk factors for breast cancer in Chinese women. We selected and genotyped 40 single nucleotide polymorphisms (SNPs) using the Sequenom iPlex platform in a female Chinese cohort of 2,901 breast cancer cases and 2,789 healthy controls. We evaluated these SNPs with the risk of breast cancer and further by estrogen receptor (ER) status, progestin (PR) status, human epidermal growth factor receptor-2 (HER-2) status, and four breast cancer subtypes (Luminal A type, Luminal B type, HER-2 overexpression type and Basal-like type). We first confirmed that the SNP rs9693444 on 8p12 was associated with breast cancer in Chinese women (P = 6.44 × 10(-4)). Furthermore, we identified four susceptibility loci that were associated with specific tumor subtypes. Statistically significant differences were detected with the association of rs6828523 (4q34.1/ADAM29) with ER-positive breast cancer (P = 1.27 × 10(-3)) and the association of rs4849887 (2q14.2) with PR-positive breast cancer (P = 1.29 × 10(-3)). Of the four breast cancer subtypes, the associations of rs12493607 (3p24.1/TGFBR2) with HER-2 overexpression in breast cancer (P = 1.09 × 10(-3)) and rs11075995 (16q12.2/FTO) with basal-like breast cancer (P = 1.64 × 10(-4)) were statistically significant. This study is the first to show that these 5 susceptibility loci (8p12, 4q34.1/ADAM29, 2q14.2, 3p24.1/TGFBR2, and 16q12.2/FTO) correlate with breast cancer (overall and specific subtypes) in Chinese women, which has improved our understanding of the genetic basis of specific breast cancer subtypes.

Enhancer of zeste 2 (EZH2) gene encodes a histone methyltransferase that constitutes the catalytic component of the polycomb repressive complex-2 (PRC2) to initiate epigenetic silencing of genes. It is reported that the expression level of EZH2 in gastric cancer tissue was highly correlated with tumor progression, however, whether EZH2 genetic variants were associated with the risk of gastric cancer remains yet unknown. In this study, we conducted a genotyping analysis for EZH2 in 311 cases of gastric cancer and 425 controls from the Chinese Han population. We found five single nucleotide polymorphisms (SNP; rs12670401, rs6464926, rs2072407, rs734005, and rs734004) of EZH2 gene were significantly associated with the risk of gastric cancer. Of which, the rs12670401 with the minor allele C and rs6464926 with the minor allele T revealed strong associations with increased gastric cancer risk [P = 0.009, adjusted odds ratio (aOR) = 1.327, 95% CI = 1.075-1.683 and P = 0.012, aOR = 1.310, 95% CI = 1.059-1.619]. The other three SNPs, rs2072407, rs734005, and rs734004 contributed to significantly reduced risk of gastric cancer (P = 0.033, aOR = 0.787, 95% CI = 0.633-0.981, P = 0.045, aOR = 0.799, 95% CI = 0.642-0.995 and P = 0.048, aOR = 0.803, 95% CI = 0.645-0.999), respectively. We further found that rs12670401 and rs6464926 were in a strong LD while rs2072407, rs734005, and rs734004 were in another. Haplotype analysis of the five SNPs showed that haplotype CCTCT reduced the risk of gastric cancer (P = 0.031 and aOR = 0.784), while haplotype GTCTC significantly elevated the risk of gastric cancer (P = 0.011 and aOR = 1.310). We concluded that EZH2 variants were significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of EZH2 gene variants in carcinogenesis of gastric cancer of the Chinese Han population., (© 2012 Wiley Periodicals, Inc.)

To evaluate the association of variants related to spermatogenesis with susceptibility to Chinese idiopathic nonobstructive azoospermia (NOA), seventeen tag single-nucleotide polymorphisms (SNPs) in CREM, ACT, KIF17b, and SPAG8 were analyzed in 361 NOA patients and 368 controls by Sequenom iplex technology. The results showed that two CREM SNPs, rs4934540 and rs22954152, were significantly associated with NOA and played protective roles against the disease (P value with Bonferroni correction = 0.00017, odds ratio [OR] = 0.624 and P = 0.012, OR = 0.686, respectively). Haplotype analysis of CREM gene variants suggested that haplotype CGTG of the SNPs, rs4934540, rs2295415, rs11592356, and rs1148247, exhibited significant protective effect against the occurrence of NOA (P = 0.001, OR = 0.659). The haplotype TATG conferred a significantly increased risk of NOA (P = 0.011, OR = 1.317). Furthermore, making use of quantitative RT-PCR, we demonstrated that relative mRNA expression of CREM in NOA patients with maturation arrest was only one-third of that in the controls with normal spermatogenesis (P < 0.0001). Our findings indicated that the polymorphisms of CREM gene were associated with NOA in the Chinese population and low CREM expression might be involved in the pathogenesis of spermatogenesis maturation arrest., (© 2014 by the Society for the Study of Reproduction, Inc.)

Purpose: To evaluate the association of the Hormad1 and Hormad2 single nucleotide polymorphisms (SNPs) variants with non-obstructive azoospermia (NOA) in the Chinese population., Methods: In the present study, we assessed 10 single nucleotide polymorphisms (SNPs) of Hormad1 and Hormad2 using Sequenom iplex technology in 361 NOA cases and 368 normal controls from Chinese population., Results: We observed no statistical differences in the distribution of allele frequencies. Further genetic model analysis and haplotype analysis also showed no significant difference between the two groups. However, we found that genotype distribution of rs718772 of Hormad2 was significantly different between the larger testis group (average testis volume ≥10 ml) and the small testis group (average testis volume <10 ml) in the NOA patients (P = 0.035)., Conclusions: In conclusion, Hormad1 and Hormad2 might not be the susceptible genes for the non-obstructive azoospermia in our study population. However, rs718772 of Hormad2 variant might be associated with testis development in NOA patients.

Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.

The purpose of this study was to investigate whether risk of gastric cancer (GC) was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We detected twenty-six SNPs in this gene cluster containing steroidogenic acute regulatory-related lipid transfer domain containing 3 (STARD3), protein phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1-like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2 (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls by Sequenom. We found no associations between genetic variations and GC risk. However, haplotype analysis implied that the haplotype CCCT of STARD3 (rs9972882, rs881844, rs11869286 and rs1877031) conferred a protective effect on the susceptibility to GC (P=0.043, odds ratio [OR]=0.805, 95% confidence intervals [95% CI]=0.643-0.992). The STARD3 rs1877031 TC genotype endued histogenesis of gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P=0.021, OR=2.882, 95% CI=1.173-7.084). We examined the expression of STARD3 in 243 tumor tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using immumohistochemical (IHC) analysis and tissue microarrays (TMA). The expression of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues and significantly correlated with gender (P=0.004), alcohol drinking (P<0.001), tumor location (P=0.007), histological type (P=0.005) and differentiation (P=0.023) in GC. We concluded that the combined effect of haplotype CCCT of STARD3 might affect GC susceptibility. STARD3 expression might be related to the tumorigenesis of GC in the Chinese population., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our genome-wide association study data set of 1,139 cases and 2,234 controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10(-13), odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10(-11)P9.37 × 10(-5)), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly downregulated in psoriatic lesions compared with the control skin (P=1.44 × 10(-6)) and uninvolved patient skin (P=2.95 × 10(-4)). Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also has a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into psoriasis pathogenesis with the involvement of the renin-angiotensin system pathway.

Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P(combined)=4.41 × 10⁻⁹ and rs1060573, P(combined)=1.28 × 10⁻⁸) and 1q24.2 (SELL, rs7531806, P(combined)=1.20 × 10⁻⁸) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.

Background: Genome-wide association studies (GWASs) have revealed a large number of genetic risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE), share susceptibility loci. Our study explores additional susceptibility loci shared by psoriasis and SLE in the Chinese Han population., Methods: In total, 20 single nucleotide polymorphisms (SNPs) in 17 previously reported psoriasis susceptibility loci and 34 SNPs from 24 previously reported SLE susceptibility loci were investigated in our initial psoriasis and SLE GWAS dataset. Among these SNPs, we selected two SNPs (rs8016947 and rs4649203) with association values of p<5×10(-2) for both diseases in the GWAS data for further investigation in psoriasis (7260 cases and 9842 controls) and SLE (2207 cases and 9842 controls) using a Sequenom MassARRAY system., Results: We found that these two SNPs (rs8016947 and rs4649203) in two loci (NFKBIA and IL28RA) were associated with psoriasis and SLE with genome-wide significance (Pcombined<5×10(-8) in psoriasis and Pcombined<5×10(-8) in SLE): rs8016947 at NFKBIA (Pcombined-psoriasis=3.90×10(-10), Pcombined-SLE=1.08×10(-13)) and rs4649203 at IL28RA (Pcombined-psoriasis=3.91×10(-12), Pcombined-SLE=9.90×10(-9))., Conclusions: These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.

Background: Recent work using genome–wide association studies (GWAS) in Chinese Han and white populations have discovered several novel psoriasis susceptibility genes., Aim: To examine whether the risk loci for psoriasis identified in previous GWAS in a white population are also associated with psoriasis in a Chinese Uygur population in Xinjiang., Methods: Genotyping analysis of eight single-nucleotide polymorphisms (SNPs) associated with psoriasis was performed for 539 patients with psoriasis and 749 controls, all of Chinese Uygur descent, using a commercial assay., Results: Two SNPs had an association with psoriasis in this Chinese Uygur population: SNP rs495337 in the gene encoding for zinc finger protein 313 (P < 0.001; OR = 0.80) and SNP rs20541 of the gene encoding for interleukin-13 (P < 0.001; OR = 0.82). In subgroup analyses, the two SNPs were significantly associated (P < 0.05) with type I psoriasis, Rs495337 showed statistically difference between positive family history of psoriasis patients and controls whereas rs20541 might preferentially associated with negative family history psoriasis patients. Interestingly, using multifactor dimensionality reduction, a significant two-locus interaction was seen between rs495337 and rs20541, with a crossvalidation consistency of 4/5 and average balanced prediction (accuracy 55.5%, P < 0.001)., Conclusions: ZNF313 and IL-13 are associated with risk for psoriasis in a Chinese Uygur population, and there is an effect of interaction between the two genes on this risk.

Background: Psoriasis is a common chronic inflammatory skin disease. IL23/Th17 is a newly confirmed pathway in psoriasis., Objective: To investigate the gene-gene interactions in IL23/Th17 pathway underlying psoriasis., Methods: A total of 299 single-nucleotide polymorphisms from 11 genes in IL23/Th17 pathway were genotyped on 1139 patients with psoriasis and 1694 controls. Multifactor dimensionality reduction and logistic regression algorithms were applied to explore the gene-gene interactions., Results: We found that there were a three-way interaction among IL21, CCR4 and TNF(χ(2) = 5.02(1), P = 0.025) and three pair-wise gene-gene interactions between IL12RB1 and CCR4(χ(2) = 11.66(4), P = 0.0201), IL22 and CCR4 (χ(2) = 11.97(4), P = 0.0176), IL12RB1 and IL6 (χ(2) = 7.31(1), P = 0.0069) in psoriasis., Conclusions: Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis., (© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.)

The aim of the study is to explore additional susceptibility factors for systemic lupus erythematosus (SLE) in Chinese Hans. Based on our previous GWAS of SLE, we performed a multistage replication study involving 3,152 cases and 7,050 controls from China to identify additional susceptibility loci for SLE by using the Sequenom MassArray system. All Chinese Han samples used in this study were obtained from doctors through collaboration with multiple hospitals in two geographic regions (central and southern China). Single-marker association analyses were performed using logistic regression with gender as a covariate in each case-control cohort. The joint analysis of all combined samples was performed using logistic regression with gender and sample cohorts as covariates. The significant association evidence for rs906868 (OR = 1.14, 95% CI 1.08-1.20, P combined = 7.71 × 10(-10)) and rs7579944 (OR = 1.13, 95% CI 1.07-1.19, P combined = 5.55 × 10(-9)) was observed, which located at 2p23.1. In this region, limb bud and heart development homolog (LBH) was the only gene indicated, suggesting LBH might be a susceptibility gene for SLE, although its function was still unknown. The results indicated that the SNP rs7579944, rs906868 at 2p23.1 showed significant association with SLE. The genes LBH which located in this loci might be the predisposing genes of SLE.

Vitiligo is an acquired pigmentary disorder characterized by loss of epidermal melanocytes. A strong association at a single nucleotide polymorphism (SNP) rs11966200 within MHC region had been identified in a recent genome-wide association study of generalized vitiligo in Chinese Han population. This study aims to investigate the relationships between SNP rs11966200 and the clinical features of generalized vitiligo in Chinese Han population. We compared the allele and genotype frequency among different vitiligo subphenotypes including age onset, extent of disease, clinical subtypes, family history of vitiligo and history of autoimmune disease. Our data showed SNP rs11966200 was associated with early-onset vitiligo (onset age ≤ 20 years) (odds ratio [OR], 1.54; p = 2.01 × 10(-13)), moderate-severe vitiligo (involved body surface ≥ 5 %) (OR, 1.17; p = 0.025), vitiligo vulgaris (OR, 1.13; p = 0.043), and focal vitiligo (OR, 0.86; p = 0.018). The study suggested that the underlying risk causal allele tagged by SNP rs11966200 might not only play important roles in the development of vitiligo, but also contribute to the diverse clinical characteristics of generalized vitiligo at least in Chinese Han population.

Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10 000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single-nucleotide polymorphisms and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM patients and 4006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic ARM patients carried significantly longer rare duplications than controls (P = 0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared with controls (P = 0.00031). Twelve chromosomal aberrations and 114 rare CNVs were observed in patients but not in 868 controls nor 11 943 healthy individuals from the Database of Genomic Variants. Importantly, these aberrations were observed in isolated ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare CNVs not only in syndromic but also in isolated ARM patients and provide a list of plausible candidate genes for the disorder.

PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis. In order to evaluate the association of the PRDM9 gene variants with defective spermatogenesis in the Chinese Han population, we assessed two single nucleotide polymorphisms (SNPs) in the PRDM9 gene (rs1874165 and rs2973631) using Sequenom iplex technology in 309 cases of severely defective spermatogenesis (199 cases with non-obstructive azoospermia and 110 cases with severe oligozoospermia) and 377 controls. The allele frequencies of the SNPs were not statistically different between the study groups and the controls (P = 0.95 in rs1874165 and P = 0.80 in rs2973631, respectively). The genetic model analysis of the two SNPs indicated that these SNPs variants may not be associated with defective spermatogenesis in the Chinese Han population.

Single-nucleotide polymorphisms (SNPs) of adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOR1) and ADIPOR2 genes contribute to the risk and progression of cancers. Here, we investigated the associations between variants of these three genes and the risk of gastric cancer. We genotyped six ADIPOQ SNPs, nine ADIPOR1 SNPs and six ADIPOR2 SNPs using the Sequenom technique in a hospital-based case-control study of patients with gastric cancer and cancer-free controls in the Chinese Han population. We found associations of certain variants with location of gastric cancer. Rs16861205 with the minor allele A in ADIPOQ, rs10773989 with the minor allele C and rs1044471 with the minor allele T in ADIPOR2 presented significant associations with a decreased risk of cardia cancer (P = 0.024, OR 0.605, 95 % CI 0.390-0.938; P = 0.015, OR 0.699, 95 % CI 0.522-0.935; and P = 0.022, OR = 0.703, 95 % CI 0.519-0.951, respectively). ADIPOQ rs16861205 with minor allele A displayed an association with an increased risk of body cancer (P = 0.010, OR 1.821, 95 % CI 1.148-2.890). Further stratified analysis of the patients indicated that there were significant correlations for rs1342387A/G (P = 0.027) and rs16861205A/G (P = 0.000) with tumor location; rs16850799A/G (P = 0.004) and rs2058033C/A (P = 0.003) with invasion depth; rs16850799A/G (P = 0.019) with the tumor-node-metastasis stage; rs16850799A/G (P = 0.016), rs1501299A/C (P = 0.005) and rs1063538C/T (P = 0.017) with alcohol consumption; rs11612414A/G (P = 0.040) and rs12733285T/C (P = 0.005) with salted food; rs1063538C/T (P = 0.043) with family history of gastric cancer; and rs11612414A/G (P = 0.029) with gender. Adiponectin expression significantly correlated with gender (P = 0.014), alcohol consumption (P = 0.037), family history (P = 0.019) and invasion depth of primary tumor (P = 0.024). Our data suggested that variants of ADIPOQ may be genetic markers conferring susceptibility to gastric cancer subtypes. These findings need to be validated in a larger panel of samples from distinct populations.

To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).

Background: Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant disorder characterised by coarse, wiry, twisted hair developed in early childhood and subsequent progressive hair loss. MUHH is a genetically heterogeneous disorder. No gene in 1p21.1-1q21.3 region responsible for MUHH has been identified., Methods: Exome sequencing was performed on two affected subjects, who had normal vertex hair and modest alopecia, and one unaffected individual from a four-generation MUHH family of which our previous linkage study mapped the MUHH locus on chromosome 1p21.1-1q21.3., Results: We identified a missense mutation in EPS8L3 (NM&#95;024526.3: exon2: c.22G->A:p.Ala8Thr) within 1p21.1-1q21.3. Sanger sequencing confirmed the cosegregation of this mutation with the disease phenotype in the family by demonstrating the presence of the heterozygous mutation in all the eight affected and absence in all the seven unaffected individuals. This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group., Conclusions: Taken together, our results suggest that EPS8L3 is a causative gene for MUHH, which was helpful for advancing us on understanding of the pathogenesis of MUHH. Our study also has further demonstrated the effectiveness of combining exome sequencing with linkage information for identifying Mendelian disease genes.

Protamine genes play important roles in DNA packaging within the sperm nucleus. In order to evaluate the association of PRM1, PRM2, KIT and KITLG variants with susceptibility to severely defective spermatogenesis, 309 male infertility patients (199 cases with non-obstructive azoospermia and 110 cases with severe oligozoospermia) and 377 controls were recruited in the Chinese Han population. This study genotyped 38 single-nucleotide polymorphisms (SNP) in PRM1, PRM2, KIT and KITLG using Sequenom iplex. The results showed that PRM1 variant rs35576928 (p.R34S) was significantly associated with severe oligozoospermia and played a protective role against the disease (P=0.0079, Bonferroni correction, OR 0.426). The dominant model (variant-containing genotypes) of the SNP was confirmed to protect against the occurrence of oligozoospermia (P=0.0078, Bonferroni correction, OR 0.387). Haplotype analysis of PRM1 and PRM2 in combination exhibited that haplotype TACCGGC exhibited a significant protective effect against the occurrence of oligozoospermia when compared with controls (P=0.002, Bonferroni correction, OR 0.602). Haplotype TACCTGC was strongly associated with risk of the clinical phenotype severe oligozoospermia (P=0.002, Bonferroni correction, OR 2.716). The findings indicated that PRM1 variant rs35576928 (p.R34S) was associated with severely defective spermatogenesis in the Chinese Han population. Male spermatogenic failure may be associated with gene variants. We demonstrated whether such genetic variation of PRM1 and PRM2 affected clinicopathological characteristics and conferred susceptibility to this entity. In this study, we found that PRM1 variant rs35576928 (Arg>Ser) played a protective role against severe oligozoospermia. The dominant model analysis (variant-containing genotypes) confirmed that the SNP was a risk factor of a spermatogenesis defect. Haplotype analysis of PRM1 and PRM2 showed that TACCGGC was a common factor protecting against severe oligozoospermia, while the haplotype TACCTGC was strongly associated with the risk of the severe oligozoospmeria. Our findings indicate that the PRM1 variant rs35576928 (Arg>Ser) is associated with spermatogenesis defect in the Chinese Han population., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)