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CD35, an important molecule implicated in inflammation and immunity, is reportedly associated with several cancers. However, very few studies have investigated the relationship between CD35 polymorphisms and hepatocellular carcinoma (HCC). The current study was conducted to investigate the association between tag SNPs in CD35 and HCC susceptibility and postoperative recurrence, in an attempt to elucidate the gene-environment interactions in HCC. A total of 1233 Chinese Han people, including 647 healthy controls and 586 HCC cases, were sampled in this study. Six Tag SNPs (rs10494885, rs2296160, rs3737002, rs3849266, rs669117, and rs7525160) of CD35 were selected using the HaploView 4.2 program and genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Overall, the mutation genotypes CC/CG of CD35 rs7525160 significantly increased the risk of HCC. Stratification analysis indicated that CD35 rs7525160 CC/CG genotypes increased HCC risk in patients younger than 65 years and were closely related to the pathological type of poor prognosis of HCC. Cox proportional hazard ratio model analysis revealed that the rs7525160 CC/CG genotype remains a significant independent risk factor for postoperative recurrence of HCC. In conclusion, CD35 rs7525160 polymorphism may contribute to the susceptibility and prognosis of HCC in the Chinese Han population. [ABSTRACT FROM AUTHOR]

The association between ALOX5AP SG13S114 polymorphism and ischemic stroke (IS) susceptibility has extensively been investigated, especially in white populations; however, the results were inconclusive. Here, we perform a meta-analysis to clarify the effect of SG13S114 variant on the IS risk in Europeans. The Web of Science, PubMed, EMBASE, and Medline were searched up to August 1st, 2016. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model. In total, 8 case control studies involved 8062 subjects were finally included in this meta-analysis. We observed a significantly decreased IS risk in persons carrying an A allele at the SG13S114 polymorphism compared with those with a T allele (A vs T, OR = 0.856, 95% CI = 0.797-0.919, p < 0.001). In addition, the results of sensitivity and cumulative meta-analysis indicated the robustness of our results. In addition, the publication bias was not detected using the funnel plot and Egger's tests. In summary, the present meta-analysis suggested that the A allele at the ALOX5AP SG13S114 polymorphism is a protective factor for the IS in the Europeans. In addition, further studies with large sample size are needed to validate the association, as well as in other ethnic groups. [ABSTRACT FROM AUTHOR]

Recently, the association between methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A polymorphism and neural tube defects (NTD) susceptibility has been widely investigated; however, the results remained inconclusive. Hence, we conducted a meta-analysis to evaluate the effect of MTHFD1 G1958A polymorphism on NTD. The relative literatures were identified by search of the electronic databases PubMed, MEDLINE, and EMBASE. The extracted data were statistically analyzed, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the association strength using Stata version 11.0 software. Finally, ten studies met our inclusion criteria, including 2,132/4,082 in NTD infants and controls; 1,402/3,136 in mothers with NTD offspring and controls; and 993/2,879 in fathers with NTD offspring and controls. This meta-analysis showed that, compared with the mothers with GG genotype, the women with AA genotype had an increased risk of NTD in their offspring, with OR values and 95 % CI at 1.39 (1.16-1.68), p < 0.001. Interestingly, fathers with AG genotype had a significant decreased risk of NTD offspring (OR = 0.79, 95 % CI = 0.66-0.94, p = 0.009). However, there was no significant association between the MTHFD1 G1958A polymorphism in NTD patients and the risk of NTD. In conclusion, the present meta-analysis provided evidence of the association between maternal MTHFD1 G1958A polymorphism and NTD susceptibility. [ABSTRACT FROM AUTHOR]

Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cells in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma. Methods: A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection. Results: Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele “C” of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P = 0.033) and genotype “CC” of rs246871 to be associated with an increased probability of HBV-associated HCC (P = 0.007). In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05). Conclusions: Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we investigated the major histocompatibility complex (MHC) class I chain-related gene B (MICB) allelic variation by sequence-based typing (SBT) in 201 healthy, unrelated Han subjects from Hunan province, southern China. Eleven MICB alleles were observed, among which MICB∗005:02 predominated with a frequency of 64.93%. Significant linkage disequilibrium (LD) was observed for 5 HLA-B-MICB and 6 MICA-MICB haplotypes. Compared with a northern Chinese Han population, several MICB-containing haplotypes appeared to be highly specific to this southern Chinese Han population. Two new MICB alleles, MICB∗005:06 and MICB∗026, were identified. Aligned with MICB∗005:02, MICB∗005:06 has a synonymous T replacement at nucleotide 762 in exon 4; MICB∗026 has probably arisen from MICB∗004:01 through a single nucleotide substitution from G to A at position 826 in exon 4, leading to an amino acid change from glutamic acid to lysine at codon 253. HLA-A∗02-C∗01-B∗46-MICA∗010-MICB∗005:02-DRB1∗09 was the most prevalent six-locus haplotype with a frequency of 8.49%. HLA-A∗30-C∗06-B∗13:02-MICA∗008:01-MICB∗005:02-DRB1∗07 appeared to be a conserved extended haplotype. Our results provide new information about MICB genetic polymorphism in Chinese Han populations, and will inform future studies of the potential role of MICB in allogeneic organ transplantation and disease susceptibility in related ethnic groups. [Copyright &y& Elsevier]

Abstract: Major histocompatibility complex class I chain-related gene B (MICB) has only been characterized for allelic variation in very few human populations. The MICB polymorphism remains largely unknown in Chinese populations. In this study, 104 healthy unrelated Han subjects recruited from central Inner Mongolia Autonomous Region, northern China, were investigated by sequence-based typing for MICB allelic variation, the association of MICB alleles with AluyMICB insertion/deletion dimorphism located in MICB intron 1, linkage disequilibrium of MICB with human leukocyte antigen (HLA)-B and MICA, and HLA-A-C-B-MICA-MICB haplotypic diversity. Ten kinds of MICB alleles were observed, among which MICB*005:02/010, MICB*002:01, and MICB*004:01 were the most frequent alleles with frequencies of 51.44, 16.35, and 11.54%, respectively. Significant linkage disequilibrium (LD) was observed for 9 of the 21 HLA-B-MICB haplotypes and 6 of the 17 MICA-MICB haplotypes with a frequency >1.5%. In particular, HLA-B*13:01 and HLA-B*13:02, both of which were frequently represented in this population, exhibited a distinct LD pattern with the MICB allele. A new MICB allele, MICB*023, was identified, which differed from MICB*005:02/010 by a single mutation of G to A at position 86 in exon 2, resulting in an amino acid change from arginine to histidine at codon 6. HLA-A*30-C*06-B*13:02-MICA*008:01-MICB*005:02/010 was the most common haplotype, with a frequency of 8.64% in this population. HLA-A*02-C*08-B*48-MICA*Del-MICB*009N demonstrated a frequency of 2.4% in this population. Our results provide for the first time data regarding the MICB genetic polymorphism in northern Chinese Han populations and will form the basis for future studies of the potential role of MICB in allogeneic organ transplantation and disease association in related ethnic groups. [Copyright &y& Elsevier]

An association between polymorphisms in the sodium taurocholate cotransporting polypeptide (NTCP) and the natural course of hepatitis B virus (HBV) infection in the Chinese Han population has been noted. However, it is not known whether these polymorphisms are associated with the risk of developing chronic HBV infection in other racial or ethnic populations. Accordingly, we conducted a candidate single nucleotide polymorphism (SNP) association study in Tibetan and Uygur HBV-infected patients. A total of 1302 subjects including 871 Tibetans and 431 Uygurs were recruited. According to their serological and clinical characteristics, each ethnic group was divided into two groups comprising spontaneous clearance individuals and persistently infected patients. Three SNPs were genotyped by a high resolution melting curve methodology. Among the SNPs, rs2296651 exhibited a minor allele frequency of < 0.01. The frequency of allele A at rs4646287 was much higher in Tibetans (9.4% for Tibetans and 4.6% for Uygurs, p < 0.001) than in Uygurs, but the frequency of allele A at rs7154439 was the opposite (15.7% for Tibetans and 20.5% for Uygurs, p = 0.002). Irrespective of race, no significant differences in the frequency distributions of the three SNP alleles or genotypes were observed between the case and clearance groups. Moreover, none of the NTCP haplotypes were statistically different between the two groups. Data from the Tibetan patients could be grouped by HBeAg status, viral load and HBV genotype; however, no significant differences were found in the SNP genotype distribution for each characteristic. In conclusion, the NTCP polymorphisms we identified tended to be ethnicity-dependent. For Tibetans and Uygurs, no association of the three SNPs (rs7154439, rs4646287 and rs2296651) and their haplotypes with HBV chronicity was observed. Examination of SNPs in NTCP for their specific associations with the course of HBV infection in other ethnic minority groups is now required. [ABSTRACT FROM AUTHOR]

Objective In recent years, sodium taurocholate cotransporting polypeptide (NTCP) was newly identified as a hepatitis B virus (HBV) receptor, which partly shed light on the reason for HBV hepatotropism and its host specificity. However, the related researches were limited to in vitro or animal experiments. Therefore, this study aimed to investigate the association of NTCP polymorphisms with HBV natural course in humans. Methods According to their serological and clinical characteristics, 933 Chinese Han individuals were divided into two major groups, 352 viral clearance controls and 581 persistently infected patients. The latter one included 186 hepatocellular carcinoma (HCC) and 395 non-HCC subjects. A total of five single nucleotide polymorphisms (SNPs) were selected from HapMap dataset and genotyped by high resolution melting (HRM) curve method. Results The rs7154439 AA genotype was observed slightly more common in viral clearance group than in persistently infected group [16 (4.5%) subjects vs. 10 (1.7%) subjects. p = 0.008, adjusted odds ratio (AOR) = 0.33, 95% confidence interval (CI) = 0.15–0.75 in a codominant model; and p = 0.006, AOR = 0.32, 95% CI = 0.14–0.72 in a recessive model]. While the rs4646287 AA genotype was observed slightly more frequent in HCC group than in non-HCC group [6 (3.2%) subjects vs. 1 (0.3%) subject. p = 0.018, AOR = 15.74, 95% CI = 1.59–155.54 in a codominant model; and p = 0.018, AOR = 15.91, 95% CI = 1.61–157.01 in a recessive model]. There were no statistically significant differences of allele or haplotype distribution between any two groups. Conclusions This study suggests that polymorphisms in the NTCP region may be associated with the natural course of HBV infection. The rs7154439 AA genotype was associated with HBV clearance, while the rs4646287 AA genotype was associated with HCC occurrence. However, considering the sample size is relatively small, larger studies, especially through multicenter collaboration will be needed to fully validate the significance of these findings. [ABSTRACT FROM AUTHOR]

Abstract: Background: Evidence showed that the SCN1A IVS5N+5G>A polymorphism might be associated with susceptibility to epilepsy with febrile seizures (EFS), however, the published data were inconclusive. Therefore, a meta-analysis was performed to estimate the overall EFS risk with the polymorphism. Methods: The PubMed and Medline were searched up to March, 2013 for studies on the association between SCN1A IVS5N+5G>A polymorphism and EFS risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by means of a genetic model free approach. The heterogeneity and sensitivity of each report and the publication bias were also performed. All the statistical analyses were done using the STATA 11.0 software. Result: A total of 6 studies with 2719 cases and 2317 controls met the selection criteria. We found significant association between SCN1A polymorphism and EFS (A vs. G: OR=1.498, 95%CI=1.138–1.972; AA vs. GG: OR=2.292, 95%CI=1.620–3.243; AG vs. GG: OR=1.414, 95%CI=1.010–1.978; recessive model: OR=1.747, 95%CI=1.119–2.728 and dominant model: OR=1.730, 95%CI=1.259–2.376). When compared with the epilepsy without febrile seizure (EWFS), the subgroup analysis stratified by ethnicity showed that the SNP was significantly associated with EFS in Caucasian (A vs. G: OR=1.505, 95%CI=1.218–1.861; AA vs. GG: OR=2.081, 95%CI=1.358–3.189; recessive model: OR=1.715, 95%CI=1.273–2.310 and dominant model: OR=1.625, 95%CI=1.096–2.410), but not in Indian and Chinese. When applying Bonferroni correction (significance was set at 0.05/20), the Caucasian still has robust association with EFS and epilepsy. Conclusion: The present meta-analysis suggests that SCN1A IVS5N+5G>A polymorphism is a risk factor of EFS and epilepsy, especially in Caucasian. [Copyright &y& Elsevier]

Abstract: In this study, the 3′untranslated region (3′UTR) of MHC class I chain-related gene A (MICA) were investigated in 104 healthy, unrelated Han individuals recruited from northern China, using PCR-sequencing method. Nine polymorphic sites were detected, which were in very strong linkage disequilibrium with each other .Seven different MICA 3′UTR alleles were identified, among which UTR1 predominated (0.6971),followed by UTR2 (0.2356). Twenty-one extended haplotypes incorporating the 3′UTR and MICA exons 2–5 were observed in this population. Phylogenetic analysis revealed the existence of two MICA lineages, each with multiple subsets. The 2 lineages were primarily linked to UTR1 and UTR2 in the 3′UTR, respectively. Ewens–Watterson homozygosity statistics at MICA coding and 3′UTR regions were consistent with neutral expectations. Our data provided for the first time the data of genetic variation in the 3′UTR of MICA gene in human populations. The findings are valuable for future studies of the mechanisms underlying MICA post-transcriptional regulation, and will inform studies of evolution of the MHC gene complex. [Copyright &y& Elsevier]

Abstract: The aim of this study was to detect the association between 2 single nucleotide polymorphisms (SNPs), rs2910164 G>C and rs3746444 T>C, in pre-miRNA (hsa-mir-146a and hsa-mir-499) and the chronic inflammation in the Chinese Han population with rheumatoid arthritis (RA). Two hundred sixty-two Han Chinese patients with RA were recruited in this study. The SNPs were genotyped by polymerase chain reaction restriction fragment length polymorphism. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the plasma concentrations of interleukin (IL)-6, tumor necrosis factor α (TNF-α), and transforming growth factor β1 (TGF-β1) were measured. There was a significant difference in the levels of CRP and ESR among different genotypes in rs3746444 (p = 0.031 and p = 0.047, respectively). The heterozygote CT had significantly higher levels of CRP and ESR compared with homozygotes CC and TT. No significant association was observed between the SNP rs2910164 and the levels of CRP, ESR, IL-6, TNF-α, and TGF-β1 (all p > 0.05). The results of this study provided the first evidence that the SNP rs3746444 in pre-miR-499 could affect the inflammatory reaction in patients with RA. The findings were significant and might contribute to the clinical assessment of inflammatory activity, which in turn may influence therapeutic decision making. [Copyright &y& Elsevier]