Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population

microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29–3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10–1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00–1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20–2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09–1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis.     

Association of CVD Candidate Gene Polymorphisms with Ischemic Stroke and Cerebral Hemorrhage in Chinese Individuals

Background

Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.

Methods

There were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.

Results

After adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.

Conclusions

The NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population.     

miR-146a and miR-196a2 Polymorphisms in Patients with Ischemic Stroke in the Northern Chinese Han Population

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3′-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case–control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199–2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery athersclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han population.     

Association Between Matrix Metalloproteinase Family Gene Polymorphisms and Ischemic Stroke: a Meta-analysis

Numerous studies have studied the relationships between matrix metalloproteinase (MMP) family gene polymorphisms and ischemic stroke. However, findings remain controversial. The objective of this study was to evaluate the relationships between MMP gene polymorphisms and ischemic stroke by using a meta-analysis. The PubMed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers, and pooled odds ratio (OR) with 95 % confidence interval (CI) were calculated. Eleven studies were enrolled, including a total of 589 cases and 494 controls of MMP-1 -1607 1G/2G; 1,817 cases and 1,731 controls of MMP-3 -1612 5A/6A; and 540 cases and 547 controls of MMP-9 -1562C/T. Under the dominant and recessive models, respectively, the overall ORs and 95 % CIs of -1607 2G were 1.54, 1.16–2.04 (P?=?0.005) and 1.25, 0.95–1.65 (P?=?0.457); the overall ORs and 95 % CIs of -1612 6A were 1.01, 0.84–1.21 (P?=?0.003) and 0.88, 0.75–1.03 (P?=?0.057); and the overall ORs and 95 % CIs of -1562T were 0.78, 0.59–1.02 (P?=?0.460) and 1.65, 0.73–3.75 (P?=?0.340). No publication bias was found in this meta-analysis. This meta-analysis showed that MMP-1 -1607 1G/2G and MMP-3 -1612 5A/6A were risk factors for ischemic stroke, while MMP-9 -1562C/T was not associated with ischemic stroke.     

Association between Polymorphisms of the IKZF3 Gene and Systemic Lupus Erythematosus in a Chinese Han Population

Objective

It has been reported that IKAROS family of zinc finger 3 (IKZF3)-deficient mice spontaneously develop human systemic lupus erythematosus (SLE)-like phenotypes and produce anti-dsDNA Ab leading to immune complex-mediated glomerulonephritis. Polymorphism of the IKZF3 gene corresponds with the susceptibility to several immune-related diseases. Our intention was to establish an association between polymorphisms in the IKZF3 gene and SLE in the Chinese Han population.

Methods

The study involved obtaining blood samples for DNA extraction and genotyping the 4 selected single-nucleotide polymorphisms (SNPs) in IKZF3, including rs12150079, rs9909593, rs907091, and rs2872507, by performing PCR restriction fragment length polymorphism analysis (PCR-RFLP). A group of 366 SLE patients were compared to 455 healthy controls.

Results

A significant decrease in frequencies of the rs907091 CC genotype and C allele appeared in the SLE patients unlike that observed in the controls (p = 0.001 and 0.015, respectively). The frequencies of the rs12150079 genotype and allele were different between the SLE patients and the control individuals, although the significance was only marginal (p = 0.046 and 0.049, respectively). In addition, a significantly low frequency of the GGCG haplotype was observed in the SLE patients, suggesting that it may provide protection against SLE (p = 0.011).

Conclusion

To the best of our knowledge, this is the first study to demonstrate an important association between polymorphisms in IKZF3 and SLE in the Chinese Han population. A strong association between rs907091 in the IKZF3 gene and SLE was identified.     

Association of Complement C5 Gene Polymorphisms with Proliferative Diabetic Retinopathy of Type 2 Diabetes in a Chinese Han Population

Purpose

To investigate the association of C5 SNPs with proliferative diabetic retinopathy (PDR) of type 2 diabetes (T2D).

Methods

A total of four C5 SNPs including rs2269067, rs7040033, rs1017119 and rs7027797 were genotyped in 400 PDR patients with T2D (cases) and 600 non- proliferative diabetic retinopathy PDR (NPDR) with T2D patients (controls) by using PCR-RFLP method. mRNA expression was examined by real-time PCR. Cytokine production was detected by ELISA.

Results

The frequency of GG genotype of C5 rs2269067 was significantly increased in cases compared with controls (Pc = 3.4×10⁻⁵, OR = 1.87). And C5 mRNA expression was significantly increased in rs2269067 GG cases as compared with CG or CC cases (P = 0.003, P = 0.001, respectively). Moreover, the production of IL-6 was significantly increased in rs2269067 GG cases compared to CG cases or CC cases (P = 0.002, P = 0.001, respectively).

Conclusions

C5 rs2269067 GG genotype confers risk for PDR of T2D in Chinese han population and is associated with an elevated C5 mRNA expression and an increased IL-6 production.     

Association of Aminoacyl-tRNA Synthetases Gene Polymorphisms with the Risk of Congenital Heart Disease in the Chinese Han Population

Aminoacyl-tRNA synthetases (ARSs) are in charge of cellular protein synthesis and have additional domains that function in a versatile manner beyond translation. Eight core ARSs (EPRS, MRS, QRS, RRS, IRS, LRS, KRS, DRS) combined with three nonenzymatic components form a complex known as multisynthetase complex (MSC).We hypothesize that the single-nucleotide polymorphisms (SNPs) of the eight core ARS coding genes might influence the susceptibility of sporadic congenital heart disease (CHD). Thus, we conducted a case-control study of 984 CHD cases and 2953 non-CHD controls in the Chinese Han population to evaluate the associations of 16 potentially functional SNPs within the eight ARS coding genes with the risk of CHD. We observed significant associations with the risk of CHD for rs1061248 [G/A; odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.81–0.99; P = 3.81×10⁻²], rs2230301 [A/C; OR = 0.73, 95%CI = 0.60–0.90, P = 3.81×10⁻²], rs1061160 [G/A; OR = 1.18, 95%CI = 1.06–1.31; P = 3.53×10⁻³] and rs5030754 [G/A; OR = 1.39, 95%CI = 1.11–1.75; P = 4.47×10⁻³] of EPRS gene. After multiple comparisons, rs1061248 conferred no predisposition to CHD. Additionally, a combined analysis showed a significant dosage-response effect of CHD risk among individuals carrying the different number of risk alleles (P _trend = 5.00×10⁻⁴). Compared with individuals with “0–2” risk allele, those carrying “3”, “4” or “5 or more” risk alleles had a 0.97-, 1.25- or 1.38-fold increased risk of CHD, respectively. These findings indicate that genetic variants of the EPRS gene may influence the individual susceptibility to CHD in the Chinese Han population.     

Association Between Single Nucleotide Polymorphisms of DOT1L Gene and Risk of Knee Osteoarthritis in a Chinese Han Population

To investigate associations between single nucleotide polymorphisms rs12982744 and rs12459350 in the DOT1L gene and knee osteoarthritis (OA) susceptibility in a Chinese Han population. DOT1L rs12982744 and rs12459350 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. A total of 605 patients with knee OA and 615 controls were enrolled in the study. GC and CC genotypes of rs12982744, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs12982744 GC heterozygotes compared with GG homozygotes was stronger in females and those aged >65 years. In contrast, the GA and AA genotypes of rs12459350 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. Our results showed that DOT1L rs12982744 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.     

Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population

Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ² = 0.15, p = 0.928 by genotype, χ² = 0.14, p = 0.711 by allele; rs763780: χ² = 2.24, p = 0.326 by genotype, χ² = 0.26, p = 0.609 by allele; rs4819554: χ² = 1.79, p = 0.409 by genotype, χ² = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation.     

There Is No Association between MicroRNA Gene Polymorphisms and Risk of Triple Negative Breast Cancer in a Chinese Han Population

Triple-negative breast cancer (TNBC) is defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It is characterized by aggressive behavior, poor prognosis and lack of targeted therapies. MicroRNA (miRNA) as a novel modulator of gene expression has played an important regulatory role in the malignancy. Dysregulation and/or mutation of the miRNAs may also contribute to the TNBC susceptibility since it is associated with the expression of ER, PR and HER2. Single nucleotide polymorphisms (SNPs) in miRNAs may be extremely relevant for TNBC. We tried to validate the hypothesis that genetic variations in miRNA are associated with TNBC development, and identify candidate biomarkers for TNBC susceptibility and clinical treatment. We screened the genetic variants in all miRNA genes listed in the public database miRBase and NCBI. A total of 23 common SNPs in 22 miRNAs, which tagged the known common variants in the Chinese Han people with a minor allele frequency greater than 0.05, were genotyped. This case-control study involved 191 patients with TNBC and 192 healthy female controls. Frequencies of SNPs were compared between cases and controls to identify the SNPs associated with TNBC susceptibility. No significant association was found between TNBC risk and the SNPs in the miRNA genes in the Chinese Han people (P>0.05), but this warrants further studies.     

Association of OX40L Polymorphisms with Sporadic Breast Cancer in Northeast Chinese Han Population

OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE), carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580) were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662), even in the validation study (P = 0.0001515). A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype A_rs844648A_rs10912580 was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003). In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541). Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.     

Detailed Analysis of Gene Polymorphisms Associated with Ischemic Stroke in South Asians

The burden of stroke is disproportionately high in the South Asian subcontinent with South Asian ethnicity conferring a greater risk of ischemic stroke than European ancestry regardless of country inhabited. While genes associated with stroke in European populations have been investigated, they remain largely unknown in South Asians. We conducted a comprehensive meta-analysis of known genetic polymorphisms associated with South Asian ischemic stroke, and compared effect size of the MTHFR C677T-stroke association with effect sizes predicted from homocysteine-stroke association. Electronic databases were searched up to August 2012 for published case control studies investigating genetic polymorphisms associated with ischemic stroke in South Asians. Pooled odds ratios (OR) for each gene-disease association were calculated using a random-effects model. We identified 26 studies (approximately 2529 stroke cases and 2881 controls) interrogating 33 independent genetic polymorphisms in 22 genes. Ten studies described MTHFR C677T (108 with TT genotype and 2018 with CC genotype) -homocysteine relationship and six studies (735 stroke cases and 713 controls) described homocysteine-ischemic stroke relationship. Risk association ORs were calculated for ACE I/D (OR 5.00; 95% CI, 1.17–21.37; p = 0.03), PDE4D SNP 83 (OR 2.20; 95% CI 1.21–3.99; p = 0.01), PDE4D SNP 32 (OR 1.57; 95% CI 1.01–2.45, p = 0.045) and IL10 G1082A (OR 1.44; 95% CI, 1.09–1.91, p = 0.01). Significant association was observed between elevated plasma homocysteine levels and MTHFR/677 TT genotypes in healthy South Asians (Mean difference (ΔX) 5.18 µmol/L; 95% CI 2.03–8.34: p = 0.001). Our results demonstrate that the genetic etiology of ischemic stroke in South Asians is broadly similar to the risk conferred in Europeans, although the dataset is considerably smaller and warrants the same clinical considerations for risk profiling.     

Endothelial NO Synthase Gene Polymorphisms and Risk of Ischemic Stroke in Asian Population: A Meta-Analysis

Background

The association between polymorphism 4b/a, T-786C and G894T in endothelial NO synthase gene (eNOS) and ischemic stroke (IS) remains controversial in Asian. A meta-analysis was performed to better clarify the association between eNOS gene and IS risk.

Methods

Based on the search of PubMed, Web of Science (ISI), CNKI (National Knowledge Infrastructure), Wan Fang Med Online and CBM (Chinese Biology Medical Literature Database) databases, all eligible case-control or cohort studies were identified. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from fixed and random effect models were calculated. Heterogeneity among studies was evaluated using the I². Meta-regression was used to explore the potential sources of between-study heterogeneity. Begg''s test was used to estimate publication bias.

Results

Our study included 27 articles, contained 28 independent case–control studies, involved a total of 3,742 cases and 3,691 controls about 4b/a, 1,800 cases and 1,751 controls about T-786C and 2,747 cases and 2,872 controls about G894T. A significant association of 4a allele with increased risk of IS was found in dominant (FEM: OR = 1.498, 95% CI = 1.329–1.689), recessive (FEM: OR = 2.132, 95% CI = 1.383–3.286) and codominant (REM: OR = 1.456, 95% CI = 1.235–1.716) models. For T-786C and G894T, there were significant associations with dominant and codominant genetic models, but not with recessive genetic model.

Conclusions

The meta-analysis indicated that eNOS gene 4b/a, T-786C, G894T polymorphism might be associated with IS.     

中国广东汉族人群核苷酸修复基因hMTH1 遗传多态性研究

为研究中国南方汉族人群核苷酸修复基因hMTH1遗传多态性,应用聚合酶链反应-单链构象多态性技术检测172名健康人外周血白细胞hMTH1基因启动子及全部5个外显子多态性,并进行DNA测序。结果发现hMTH1基因启动子及外显子1序列保守,未见突变;外显子2第73位碱基存在T→C杂合型突变,基因型TT和TC频率分别为93.02%、6.98%,等位基因T和C频率分别为96.51%、3.49％;外显子3第45位遗传密码存在T→C杂合型突变,基因型TT和TC频率分别为95.35%、4.65%,等位基因T和C频率分别为97.67%、2.33%,该多态性为首次发现;外显子4第83位遗传密码存在G→A杂合型突变,基因型GG和GA频率分别为89.53%、10.47%,等位基因G和A频率分别为94.77%、5.23％;外显子5第119位氨基酸遗传密码存在C→T杂合型突变,基因型CC和CT频率分别为95.93%、4.07%,等位基因C和T频率分别为97.97%、2.03％。Abstract: In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population, the polymorphisms of the gene’s promoter and its five exons among peripheral blood lymphocytes of 172 Chinese Han people were analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1 gene were conserved. A T to C polymorphism was detected at the 73th base in exon2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The allelic frequencies of T and C were 96.51% and 3.49％, respectively. A T to C polymorphism was detected at codon 45 in exon3, which was first reported. The genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A polymorphism was detected at codon 83 in exon4. The genotype frequencies of GG and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A were 94.77% and 5.23％, respectively. A C to T polymorphism was detected at codon 119 in exon5. The genotype frequencies of CC and CT were 95.93% and 4.07%, respectively. The allelic frequencies of C and T were 97.97% and 2.03％, respectively.     

FCRL3 Gene Polymorphisms Confer Autoimmunity Risk for Allergic Rhinitis in a Chinese Han Population

Background

Heredity and environmental exposures may contribute to a predisposition to allergic rhinitis (AR). Autoimmunity may also involve into this pathologic process. FCRL3 (Fc receptor-like 3 gene), a novel immunoregulatory gene, has recently been reported to play a role in autoimmune diseases.

Objective

This study was performed to evaluate the potential association of FCRL3 polymorphisms with AR in a Chinese Han population.

Methods

Five single-nucleotide polymorphisms of FCRL3, rs945635, rs3761959, rs7522061, rs10489678 and rs7528684 were genotyped in 540 AR patients and 600 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele, genotype and haplotype frequencies were compared between patients and controls using the χ2 test. The online software platform SHEsis was used to analyze their haplotypes.

Results

This study identified three strong risk SNPs rs7528684, rs10489678, rs7522061 and one weak risk SNP rs945635 of FCRL3 in Chinese Han AR patients. For rs7528684, a significantly increased prevalence of the AA genotype and A allele in AR patients was recorded. The frequency of the GG genotype and G allele of rs10489678 was markedly higher in AR patients than those in controls. For rs7522061, a higher frequency of the TT genotype, and a lower frequency of the CT genotype were found in AR patients. Concerning rs945635, a lower frequency of the CC genotype, and a higher frequency of G allele were observed in AR patients. According to the analysis of the three strong positive SNPs, the haplotype of AGT increased significantly in AR cases (AR = 38.8%, Controls = 24.3%, P = 8.29×10-14, OR [95% CI] 1.978 [1.652~2.368]).

Conclusions

This study found a significant association between the SNPs in FCRL3 gene and AR in Chinese Han patients. The results suggest these gene polymorphisms might be the autoimmunity risk for AR.     

Correlations between ASCC3 Gene Polymorphisms and Chronic Hepatitis B in a Chinese Han Population

We have previously identified 8 SNPs in Han Chinese HBV carriers that are associated with disease progression. Although not well studied, genetic factors may also play a significant role in developing chronic HBV disease after exposure. We extend the effect of these eight SNPs on persistent HBV infection in this study. A total of 875 unrelated Han Chinese, 493 chronic hepatitis B subjects (CHB) and 382 HBV clearance individuals (Clear), were recruited from Hubei Province from September 2007 to March 2010. SNPs were verified by using TaqMan 7900HT Sequence Detection System. By using multiple logistic regression analysis, each of the 8 SNP associations was tested using 3 different genetic models (Dominant, Recessive and Additive model), in 4 types of analyses (full sample, men, women, age stratified). A Bonferroni correction was used to account for multiple statistical tests for each SNP association (P<0.05/8 = 0.0063). A significant correlation was observed at SNP rs10485138 located in ASCC3 gene in female patients (OR, 0.445; 95% CI, 0.253–0.784; P = 0.005). Females bearing C allele infected by HBV had an increased susceptibility to CHB compared with those T allele carriers. Our results indicated that SNP rs10485138 located in ASCC3 gene was associated with persistent HBV infection in Han Chinese.     

Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case–control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p?<?1?×?10^?8) and rs17118 in XYLB gene located on chromosome 3p21 (p?<?1?×?10^?6) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR?=?2.02, 95 % CI?=?1.35–3.03) or rs17118 AA genotype (OR?=?1.50, 95 % CI?=?1.17–1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR?=?2.78, 95 % CI?=?1.59–4.86) and in individuals without diabetes (OR?=?1.93, 95 % CI?=?1.27–2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR?=?1.73, 95 % CI?=?1.08–2.78) and for individuals without diabetes (OR?=?1.52, 95 % CI?=?1.17–1.98) or non-smoker (OR?=?1.59, 95 % CI?=?1.16–2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.