Polymorphisms of ECE1 May Contribute to Susceptibility to Ischemic Stroke in Han Chinese of Northern China

Endothelin (ET) converting enzyme 1 (ECE1) is well known for its critical role in the process of ET. Recent studies have demonstrated that two genetic variants of ECE1 gene, rs212528 and rs213045 (C338A), are associated with hypertension and atherosclerosis formation. To investigate the association between the ECE1 gene polymorphisms and ischemic stroke (IS) in Chinese population. With a candidate loci strategy, we conducted a case–control study involving 381 IS cases and 366 non-IS controls in Han population of the Northern China. Two single nucleotide polymorphisms of ECE1 were genotyped and assessed the association with the risk of IS. Furthermore, stratified analyses were also carried out to evaluate the association between the gender or two etiologic subtypes [small-artery occlusion (SAO) and large-artery atherosclerosis (LAA)] and IS. Compared with rs213045 G homozygote, rs213045 TG genotype and rs213045 TT/TG genotypes are in dominant model significantly increased the risk of IS [adjusted odds ratio (OR) = 1.47, 95 % confidence interval (CI) = 1.04–2.07, P = 0.03; adjusted OR = 1.43, 95 % CI = 1.04–1.99, P = 0.029, respectively]. However, we did not find the significant association between the ECE1 gene polymorphisms and SAO or LAA of IS in this study. Our results indicated that ECE1 gene polymorphisms may contribute to the susceptibility of IS in Han population of the Northern China.     

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.     

The genetic contribution of CIDEA polymorphisms, haplotypes and loci interaction to obesity in a Han Chinese population

To investigate the association of tag-SNPs and haplotype structures of the CIDEA gene with obesity in a Han Chinese population. Five single nucleotide polymorphisms (SNPs) (rs1154588/V115F, rs4796955/SNP1, rs8092502/SNP2, rs12962340/SNP3 and rs7230480/SNP4) in the CIDEA gene were genotyped in a case–control study. Genotyping was performed using the sequenom matrix-assisted laser desorption/ionization time-of-flight mass spectrometry iPLEX platform. There were significant differences between the obese and control groups in genotype distributions of V115F (P < 0.001), SNP1 (P = 0.006) and SNP2 (P = 0.005). Carriers of V115F-TT, SNP1-GG and SNP2-CC genotypes had a 2.84-fold (95 % CI 1.73–4.66), 2.19-fold (95 % CI 1.09–4.38) and 4.37-fold (95 % CI 1.21–15.08) increased risk for obesity, respectively. Haplotype analysis showed that GTTC (SNP1/SNP2/V115F/SNP4) had 1.41-fold (95 % CI 1.02–1.95) increased risk for obesity; whereas, haplotype TTGC had 0.48-fold (95 % CI 0.24–0.96) decreased risk for obesity. Using the multifactor dimensionality reduction method, the best model including SNP1, SNP2, V115F and SNP4 polymorphisms was identified with a maximum testing accuracy to 59.32 % and a perfect cross-validation consistency of 10/10 (P = 0.011). Logistic analysis indicated that there was a significant interaction between SNP1 and V115F associated with obesity. Subjects having both genotypes of SNP1/GG and V115F/TT were more susceptible to obesity in the Han Chinese population (OR 2.66, 95 %: 1.22–5.80). Genotypes of V115F/TT, SNP1/GG and SNP2/CC and haplotype GTTC of CIDEA gene were identified as risk factors for obesity in the Han Chinese population. The interaction between SNP1 and V115F could play a joint role in the development of obesity.     

TNFAIP3 gene polymorphisms confer risk for Behcet’s disease in a Chinese Han population

The tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene polymorphisms have recently been reported to be associated with the susceptibility to several immune-related diseases. This study was performed to evaluate the potential association of TNFAIP3 polymorphisms with Behcet’s disease (BD) in a Chinese Han population. Five single-nucleotide polymorphisms (SNPs), rs10499194, rs610604, rs7753873, rs5029928, and rs9494885 of TNFAIP3 were genotyped in 722 BD patients and 1,415 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele and genotype frequencies were compared between patients and controls using the χ ² test. The results showed a significantly increased prevalence of the rs9494885 TC genotype and C allele in BD patients compared with controls (Bonferroni corrected p (p _c) = 1.83 × 10^?10, odds ratio (OR) [95 % CI] 2.03 [1.65–2.49]; p _c = 8.35 × 10^?10, OR [95 % CI] 1.81 [1.51–2.18], respectively).The frequency of the TT genotype and T allele of rs9494885 was markedly lower in BD patients than that in controls (p _c = 1.23 × 10^?10, OR [95 % CI] 0.50 [0.40–0.61]; p _c = 8.35 × 10^?10, OR [95 % CI] 0.55 [0.46–0.66], respectively). For rs10499194, a higher frequency of the CC genotype (p _c = 0.015, OR [95 % CI] 1.96 [1.30–2.97]) and C allele (p _c = 0.005, OR [95 % CI] 1.92 [1.28–2.90]), and a lower frequency of the TC genotype (p _c = 0.015, OR [95 % CI] 0.51 [0.34–0.77]) and T allele (p _c = 0.005, OR [95 % CI] 0.52 [0.35–2.97]) were found in BD patients. Concerning rs7753873, a higher frequency of the AC genotype (p _c = 0.015, OR [95 % CI] 1.49 [1.17–1.91]) and C allele (p _c = 0.025, OR [95 % CI] 1.39 [1.11–1.76]), and a lower frequency of the AA genotype (p _c = 0.03, OR [95 % CI] 0.68 [0.53–0.87]) and A allele (p _c = 0.025, OR [95 % CI] 0.72 [0.57–0.91]) were observed in BD patients. This study identified one strong risk SNP rs9494885 and two weak risk SNPs rs10499194 and rs7753873 of TNFAIP3 in Chinese Han BD patients.     

Polymorphisms in <Emphasis Type="Italic">VEGF-A</Emphasis> are associated with COPD risk in the Chinese population from Hainan province

In this study, we examined and validated how common variants contribute to susceptibility to chronic obstructive pulmonary disease (COPD) in the Han Chinese population. Here, we genotyped 18 nucleotide polymorphisms and evaluated their association with COPD using chi-square test and genetic model analysis (246 COPD patients and 350 controls), and found three SNPs that might cause a predisposition to COPD. Both rs3025030 and rs3025033 are located on chromosome 6 in VEGF-A. We found one risk allele ‘C’ from rs3025030 and another ‘G’ from rs3025033 using the log-additive model (OR 1.40; 95% CI 1.05–5.96; P = 0.022), (OR 1.38; 95% CI 1.03–1.84; P = 0.03). We also found another risk allele ‘A’ of rs9296092 in gene region ZBTB9-BAK1 by the allele model (OR 2.63; 95% CI 1.27–5.45; P = 0.0078), (adjusted OR 3.53; 95% CI 1.12–11.11; P = 0.031). We found a risk haplotype ‘CG’ associated with the risk of COPD (OR 1.39; 95% CI 1.04–1.86; P=0.028). Our results when compared with previous studies showed significant association between VEGF-A polymorphism and COPD. We also identified rs9296092 as a risk factor for COPD.     

SORL1 Is Associated with the Risk of Late-Onset Alzheimer’s Disease: a Replication Study and Meta-Analyses

The sorting-related receptor gene (SORL1) has been defined as an interesting candidate gene for Alzheimer’s disease (AD). Recently, one novel variant, rs11218343, within SORL1 was reported to be related to late-onset Alzheimer’s disease (LOAD) in Caucasians, Korean, and Japanese. The aim of this case–control study is to investigate whether SORL1 rs11218343 contributes to susceptibility for LOAD in Chinese. Furthermore, our data, along with previously studies, were pooled for determining the risk of the rs11218343 polymorphism on LOAD. The rs11218343 polymorphism was genotyped in the 2350 independent subjects from Northern Han Chinese population (including 992 cases and 1358 age- and gender-matched controls). Result of the case–control study showed the association between rs11218343 polymorphism and the risk of LOAD in a Northern Han Chinese population (recessive model: odds ratio (OR)?=?0.641, 95 % confidence interval (CI)?=?0.464–0.884, P?=?0.007; additive model: OR?=?0.873, 95 % CI?=?0.765–0.996, P?=?0.043). The results of meta-analysis in subgroups (Caucasian and Asian) and the whole showed that the minor allele (C allele) within rs11218343 played a protective effect on AD risk (OR (95 % CI), 0.77 (0.72–0.83), 0.85 (0.79–0.91), 0.81 (0.76–0.85), respectively). In conclusion, the C allele in SORL1 rs11218343 may be a protective factor for LOAD in both Caucasian and Han Chinese.     

Apo A5 −1131T/C, FgB −455G/A, −148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects

The Apolipoprotein A5 (APO A5) ?1131T/C, fibrinogen β (FgB) ?455G/A, ?148C/T, and cholesteryl ester transfer protein (CETP) TaqIB gene polymorphisms have been indicated to be associated with the coronary artery disease (CAD) risk, but the individual study results are still inconsistent. To explore the relationship between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD in the Chinese population, the current meta-analysis involving 15,055 subjects from 40 individual studies was conducted. The pooled odds ratio (OR) for the association between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD and its corresponding 95 % confidence interval (95 % CI) were evaluated by random or fixed effect model. A significant association between APO A5 ?1131T/C gene polymorphism and CAD in the Chinese population was found under an allelic (OR: 1.33, 95 % CI: 1.22–1.44, P < 0.00001), recessive (OR: 1.67, 95 % CI: 1.25–2.25, P = 0.0006), dominant (OR: 0.820, 95 % CI: 0.767–0.876, P = 1.0 × 10^?10), homozygous (OR: 2.36, 95 % CI: 1.55–3.58, P < 0.0001) and heterozygous genetic models (OR: 1.136, 95 % CI:1.075–1.200, P = 1.0 × 10^?10). A significant association between FgB ?455G/A gene polymorphism and CAD was also detected in the Chinese population under an allelic (OR: 1.50, 95 % CI: 1.25–1.81, P < 0.0001), dominant (OR: 0.864, 95 % CI: 0.819–0.912, P = 1.0 × 10^?10), homozygous (OR: 1.616, 95 % CI: 1.213–2.152, P = 0.001) and heterozygous genetic models (OR: 1.245, 95 % CI:1.138–1.361, P = 1.0 × 10^?10). No significant association was found between them under a recessive genetic model (OR: 1.124, 95 % CI: 0.844–1.497, P = 0.424). A significant association was also found between FgB ?148C/T gene polymorphism and CAD in the Chinese population under an allelic (OR: 1.34, 95 % CI: 1.06–1.71, P = 0.02), recessive (OR: 1. 65, 95 % CI: 1.02–2.69, P = 0.04), dominant (OR: 0.924, 95 % CI: 0.872–0.978, P = 0.007) and homozygous genetic models (OR: 0.968, 95 % CI: 0.942–0.995, P = 0.018). No significant association was found between them under a heterozygous genetic model (OR: 0.979, 95 % CI: 0.937–1.023, P = 0.342). In the whole Chinese population, no significant association between the CETP TaqIB gene polymorphism and CAD was found under an allelic (OR: 1.17, 95 % CI: 0.94–1.45, P = 0.15), dominant (OR: 1.46, 95 % CI: 0.80–2.67, P = 0.22) or recessive genetic models (OR: 0.68, 95 % CI: 0.32–1.44, P = 0.31). However, in the subgroup analysis stratified by ethnicity, there was a significant association between them under an allelic (OR: 1.27, 95 % CI: 1.07–1.52, P = 0.007) and dominant genetic model (OR: 2.04, 95 % CI: 1.49–2.79, P < 0.00001) in the Han subgroup. In the Chinese population, the APO A5 ?1131T/C and FgB ?455G/A, ?148C/T gene polymorphisms were implied to be associated with CAD susceptibility. The APO A5 ?1131C, FgB ?455A, and ?148T alleles might confer susceptibility to CAD. CETP TaqIB gene polymorphism was suggested to be associated with CAD susceptibility in the Chinese Han population. Carriers with B1 allele of CETP TaqIB gene might be predisposed to CAD in the Chinese Han population.     

Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis

This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04–1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03–1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05–1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08–1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01–3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09–4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.     

Combined effects of the BDNF rs6265 (Val66Met) polymorphism and environment risk factors on psoriasis vulgaris

Smoking, alcohol consumption and higher body mass index (BMI) are well established risk factors for psoriasis and also associated with the clinical traits of the disease. And the genetic influences on these three risk factors indeed exist. Previously studies have demonstrated these risk factors related genetic variants may also play a role in the development of risk factors-related diseases. Then we performed a hospital-based study in order to evaluate the combined effect of the risk factors and their related polymorphism rs6265 in brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and clinic traits. The case–control study involved 660 subjects including 345 cases and 315 controls in Chinese Han population. The variant of rs6265 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher BMI (≥25), smoking and alcohol consumption were risk factors for PV, and the estimated ORs were 1.63(95 % confidence interval (CI); 1.12–2.37), 2.09(95 % CI; 1.44–3.03) and 1.65(95 % CI; 1.15–2.37) respectively. Genotype and allele distributions did not differ significantly between case and control. However, we found combined effect of rs6265 genotype (GG) and higher BMI (≥25) increased risk of PV (OR = 2.09; 95 % CI, 1.02–4.28; P < 0.05; adjusted OR = 3.19; 95 % CI, 1.37–7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09–6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10–1.40; P < 0.05). But none such significant combined effect was observed between others genotype (AA and AG) and other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese Han population.     

Association between BH3 interacting domain death agonist (BID) gene polymorphism and ossification of the posterior longitudinal ligament in Korean population

The purpose of this study was to investigate single nucleotide polymorphisms (SNPs) of the BH3 interacting domain death agonist (BID) gene as a risk factor in Korean patients with ossification of the posterior longitudinal ligament (OPLL). To investigate the genetic association, two coding SNPs (rs8190315, Ser10Gly; rs2072392, Asp60Asp) of BID were genotyped in 157 OPLL patients and 209 control subjects. SNPStats, SNPAnalyzer Pro, Helixtree, and Haploview 4.2 programs were used for association analysis. Multiple logistic regression models (codominant, dominant, and recessive) were calculated for the odds ratios (ORs), 95 % confidence intervals (CIs), and corresponding P values. For multiple testing, Bonferroni correction was performed. After Bonferroni correction, genotype analysis of both rs8190315 and rs2072392 showed association between the OPLL group and the control group in the codominant model (P = 0.042, OR 1.86, 95 % CI 1.10–3.15). A complete linkage disequilibrium block was estimated between the two SNPs. Both of the G allele of rs8190315 and C allele of rs2072392 were strongly associated with an increased risk in the development of OPLL (P = 0.0052, OR 2.66, 95 % CI 1.51–4.68). These results suggest that BID is associated with OPLL, and both the G allele of a missense SNP (rs8190315, Ser10Gly) and C allele of a synonymous SNP (rs2072392, Asp60Asp) are risk factors for the development of OPLL in Korean population.     

VEGF +936C/T and +460C/T gene polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the VEGF +936C/T (rs833061) and +460C/T (rs3025039) gene polymorphisms and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, we performed a meta-analysis. The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for case–control studies that were published up to January 2013. Data were extracted and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Ultimately, six studies were included, comprising 1006 oral cancer cases and 1016 controls. Overall, the pooled OR for VEGF +936 T allele carriers (TC + TT) versus the wild-type homozygotes (CC) was 1.28 (95 % CI 1.04–1.58; P = 0.228 for heterogeneity), the pooled OR for TT versus CC was 1.64 (95 % CI 1.34–1.98; P = 0.315 for heterogeneity), and the pooled OR for the T allele versus the C allele was 1.42 (95 % CI 1.22–1.76; P = 0.286 for heterogeneity). In the stratified analysis by ethnicity, significant risks were found among Caucasians but not Asians. However, there were no associations between VEGF +460C/T and oral cancer risk in only two of the included studies. In conclusion, this meta-analysis demonstrates that the VEGF +936 T allele may be associated with an increased risk of oral cancer, especially among Caucasian populations.     

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95  % CI, 1.01–2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO (>246 g/day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3–5.46; p = 0.007; p for [CHO × PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI, 1.19–8.89; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population.     

Relationships of LDLR genetic polymorphisms with cerebral infarction: a meta-analysis

This meta-analysis was undertaken to identify the relationships between genetic polymorphisms in the LDLR gene and the risk of cerebral infarction. The Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) were searched for relevant articles without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (OR) with their corresponding 95 % confidence interval (CI) were calculated. Eight case–control studies with a total of 4,655 patients with cerebral infarction and 15,920 healthy control subjects were included in our meta-analysis. Five common polymorphisms in the LDLR gene were evaluated, including rs11669576 A > T, rs1433099 C > T, rs5925 C > T, rs688 C > T, rs1122608 T > G in the LDLR gene. The results of this meta-analysis revealed that cerebral infarction patients had a higher frequency of LDLR genetic polymorphisms than that of healthy controls (allele model: OR 1.17, 95 % CI 1.05–1.30, P = 0.004; dominant model: OR 1.18, 95 % CI 1.05–1.33, P = 0.007; homozygous model: OR 1.50, 95 % CI 1.03–2.16, P = 0.032; respectively), especially for the rs11669576 A > T, rs1433099 C > T and rs5925 C > T polymorphisms. Among different ethnic subgroups, the results demonstrated positive correlations between LDLR genetic polymorphisms and an increased risk of cerebral infarction among both Asians and Caucasians under the allele and dominant models (all P < 0.05). Our findings indicate that LDLR genetic polymorphisms may be strongly involved in the pathogenesis of cerebral infarction, especially the rs11669576 A > T, rs1433099 C > T, rs5925 C > T polymorphisms.     

A novel major histocompatibility complex locus confers the risk of premature coronary artery disease in a Chinese Han population

Several novel loci have been proved to be associated with coronary artery disease and/or myocardial infarction risk by genome-wide association studies, however, the available coronary artery disease risk variants explain only a small proportion of the predicted genetic heritability of the disease. Recently, a novel coronary artery disease locus on chromosome 6p21.3 in the major histocompatibility complex was identified in an European population. We hereby investigated whether this single nucleotide polymorphisms (rs3869109) confers the risk of premature coronary artery disease in a Chinese Han population. A total of 422 patients were studied including 210 cases with coronary stenosis ≥50 % or previous myocardial infarction (male <55 years and female <65 years) and 212 controls without documented coronary artery disease. Ligase detection reaction was performed to detect rs3869109. The 3 genotypes AA, AG, and GG were present in rs3869109. There were significant differences between the control and premature coronary artery disease groups in the frequencies of the rs3869109 variants and alleles (all P < 0.05). The distribution of 3 genotypes and alleles at rs3869109 does not differ between women and men (all P > 0.05). There was a significant association between rs3869109 genotypes and the severity of premature coronary artery disease (P = 0.038). Multivariate logistic regression showed that carriers with AG and GG genotypes at rs3869109 have a higher risk of premature coronary artery disease than carriers of AA genotype (odds ratio [OR] 1.997, 95 % CI: 1.166–3.419, P = 0.012; OR 1.695, 95 % CI: 1.044–2.752, P = 0.033; respectively). Our results indicate that the rs3869109 variants are associated with premature coronary artery disease in a Chinese Han population, suggesting this genetic risk marker is useful in early coronary artery disease risk prediction.     

Genetic polymorphisms in VDR,ESR1 and ESR2 genes may contribute to susceptibility to Parkinson’s disease: a meta-analysis

We conducted this meta-analysis of relevant case–control studies to investigate the relationships between genetic polymorphisms in VDR, ESR1 and ESR2 genes to the susceptibility of Parkinson’s disease (PD). A search on electronic databases without any language restrictions was conducted: MEDLINE (1966–2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980–2013), CINAHL (1982–2013), Web of Science (1945–2013) and the Chinese Biomedical Database (1982–2013). Meta-analysis was performed using the STATA statistical software. Crude odds ratio (OR) with their 95 % confidence interval (95 % CI) was calculated. Fourteen case–control studies with a total of 3,689 PD patients and 4,627 healthy subjects were included in our meta-analysis. The results of our meta-analysis demonstrated that the VDR genetic polymorphisms might be closely related to increased risks of PD (allele model: OR = 1.18, 95 % CI 1.09–1.29, P < 0.001; dominant model: OR = 1.37, 95 % CI 1.16–1.63, P < 0.001; respectively), especially for the polymorphisms rs7976091 and rs10735810. Our findings also illustrated that ESR1 genetic polymorphisms might increase the risk of PD (allele model: OR = 1.56, 95 % CI 1.17–2.07, P = 0.002; recessive model: OR = 1.93, 95 % CI 1.33–2.80, P < 0.001; homozygous model: OR = 1.35, 95 % CI 1.02–1.79, P = 0.038; heterozygous model: OR = 2.04, 95 % CI 1.36–3.07, P = 0.001; respectively), especially for the polymorphisms rs2234693 and rs9340799. Furthermore, we found significant correlations of ESR2 genetic polymorphisms with the risk of PD (allele model: OR = 1.78, 95 % CI 1.19–2.67, P = 0.005; recessive model: OR = 1.93, 95 % CI 1.15–3.27, P = 0.014; homozygous model: OR = 1.77, 95 % CI 1.09–2.89, P = 0.022; heterozygous model: OR = 1.88, 95 % CI 1.08–3.27, P = 0.025; respectively), especially for the rs1256049 polymorphism. Our meta-analysis suggests that genetic polymorphisms in VDR, ESR1 and ESR2 genes may contribute to increased risks for PD.     

Genetic variation in members of the leukotrienes biosynthesis pathway confers risk of ischemic stroke in Eastern Han Chinese

This study was aimed to explore the association of genetic variation in members of the leukotrienes biosynthesis pathway as potential mediators with ischemic stroke (IS) risk in Eastern Han Chinese. A case-control study of was conducted with five selected single nucleotide polymorphisms (SNPs). In the single-locus analysis, carriers of C allele of rs730012 in LTC4S were more susceptible to IS (OR, 1.28; 95% CI, 1.02–1.60; P=0.033). Under the recessive genetic model, ALOX5 rs2029253 variant reduced IS risk (adjusted OR, 0.78; 95% CI, 0.60–1.00; P=0.048) while LTA4H rs6538697 and LTC4S rs730012 variants increased (adjusted OR, 1.66; 95% CI, 1.04–2.64; P=0.032 and adjusted OR, 3.63; 95% CI, 1.01–13.05; P=0.048, respectively). However, there was no evidence of association between all five SNPs and IS risk after correction for multiple testing. In combined analysis of multiple genes and loci, individuals with ALOX5AP rs12429692 T allele, ALOX5 rs2029253 A allele, and LTA4H rs6538697 C allele suggested a significantly increased susceptibility to IS (adjusted OR, 1.70; 95% CI, 1.07–2.69; P=0.024). The present study suggested gene–gene interactions in leukotrienes pathway could exert influences on the risk of IS.     

The association of rs1149048 polymorphism in Matrilin-1(MATN1) gene with adolescent idiopathic scoliosis susceptibility: a meta-analysis

Several previous studies have evaluated the association between rs1149048 polymorphism in the matrilin-1 gene (MATN1) and the risk of adolescent idiopathic scoliosis (AIS). However the results of those studies were inconsistent. We conducted this meta-analysis to assess whether rs1149048 polymorphism was involved in the risk of AIS and evaluated the associations in different ethnicities. Electronic databases, such as: PubMed, EMBASE, WANFANG databases in any languages up to Dec 2012 were searched to assess the association between rs1149048 polymorphism and AIS. Meta-analysis was performed by STATA 12.0 software to estimate the pooled odds ratio (OR) and the 95 % confidence interval (CI). Finally four papers including five studies which involved 1436 AIS patients and 1,879 controls were identified for this meta-analysis. The results showed that G allele of the rs1149048 was significantly associated with increased AIS risk [OR = 1.13, 95 % CI (1.02–1.25), P = 0.023]. As for genotype (GG vs. GA + AA), homozygous GG genotype was also found to be a risk factor of developing AIS. The subgroup meta-analysis results showed G allele and GG genotype were significantly associated with AIS in Asian group but not in Caucasian group. Neither Egger’s test nor Begg’s test found evidence of publication bias in current study (P > 0.05). In summary, this meta-analysis found an overall significant association of rs1149048 polymorphism with risk of AIS, especially in Asian population. The relationship between rs1149048 polymorphism and AIS in other ethnic population is needed to be investigated.     

A commonly carried genetic variant,rs9616915, in SHANK3 gene is associated with a reduced risk of autism spectrum disorder: replication in a Chinese population

Autism spectrum disorder (ASD) is one of neurodevelopmental disorders with highly heritability. Recently, abnormality at the synapse is found to be important etiology of ASD. SHANK3 gene is suggested as a strong candidate gene for the pathogenesis of ASD, because it is essential for normally synaptic structure and function. We performed a case–control study to identify association between rs9616915 of the SHANK3 gene and ASD in a Chinese population. Genomic DNA was extracted from oral swabs samples of 212 patients and 636 controls and the SNP genotypes were determined by a polymerase chain reaction–restriction fragment length polymerase assay. Significant difference in genotype distribution of rs9616915 was observed between cases and controls by Pearson’s χ ² test (χ ² = 6.92, P = 0.031). Genetic analysis of heterozygous model, dominant model and additive model showed an association of the C allele of the rs9616915 with ASD (e.g., additive model, OR 0.582, 95 % CI 0.359–0.942, P = 0.028). In conclusion, our results suggested that this commonly genetic variant in SHANK3 gene strikingly decreased the risk of ASD in China.     

Oxidative Stress-Related Genes in Type 2 Diabetes: Association Analysis and Their Clinical Impact

Worldwide prevalence of diabetes mellitus motivates a number of association studies to be conducted throughout the world. Eleven polymorphisms from nine candidate genes in oxidative stress pathway have been analyzed in eastern Indian type 2 diabetic patients (n = 145) and healthy controls (n = 100). Different biochemical parameters were also analyzed for their association with the disease. Significant associations were observed for rs2070424 A>G SOD1 (OR 3.91, 95% CI 2.265–8.142, P < 0.001), rs854573 A>G PON1 (OR 3.415, 95% CI 2.116–5.512, P < 0.001), rs6954345 G>C PON2 (OR 3.208, 95% CI 2.071–4.969, P < 0.001), RAGE rs1800624 ?374 T>A (OR 3.58, 95% CI 2.218–5.766, P < 0.001), and NOS3 ?786 T>C (OR 3.75, 95% CI 2.225–6.666, P < 0.001). Haplotype containing two risk alleles of PON1 and PON2 genes was significantly associated with disease (OR 8.34, 95% CI 1.554–44.804, P < 0.002). Our results suggest that carriers of major and efficient alleles of oxidative stress genes are more likely to survive the comorbid complications and single copy of risk allele is sufficient for developing the disease.