Associations of CYP4A11 gene–gene and gene–smoking interactions with essential hypertension in the male eastern Chinese Han population

Objectives: The aim of this study was to investigate the impact of CYP4A11 single-nucleotide polymorphisms (SNP), additional gene–gene and gene–environment interactions on essential hypertension (EH) risk. Methods: A total of 1648 participants (788 males, 860 females), with a mean age of 56.1 ± 14.1 years old, were selected, including 820 EH patients and 828 normotension subjects. Logistic regression was performed to investigate association of SNPs within CYP4A11 gene with high DBP, high SBP and EH risk, and generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene interaction and gene–smoking interaction. Results: Logistic regression analysis showed that EH risk was significantly higher in carriers of C allele of the rs1126742 polymorphism than those with TT genotype (TC+CC versus TT, adjusted OR (95%CI) = 1.56 (1.24–1.91). In addition, we also found that EH risk was also significantly higher in carriers of G allele of the rs3890011polymorphism than those with CC genotype (CG+ GG versus CC, adjusted OR (95%CI) = 1.31 (1.15–2.03). GMDR analysis indicated a potential gene–gene interaction between rs1126742 and rs3890011 and a gene–environment interaction between rs1126742 and smoking. We found that subjects with TC or CC of rs1126742 and CG or GG of rs3890011genotype have the highest EH risk, OR (95%CI) was 2.52 (1.28–3.57). Smokers with TC or CC of rs1126742 genotype have the highest EH risk, OR (95%CI) was 2.20 (1.28–3.40). Conclusions: Gene–gene interaction between rs1126742 and rs3890011 and gene–environment interaction between rs1126742 and smoking were associated with increased EH risk.     

Gene–gene interaction between CD40 and CD226 gene on systemic lupus erythematosus in the Chinese Han population

The aim of the study is to investigate the impact of CD40 and CD226 gene single-nucleotide polymorphism (SNP) and additional gene–gene interaction on systemic lupus erythematosus (SLE) risk in Chinese Han populations. Three SNPs were selected for genotyping in the case–control study: rs4810485, rs763361, and rs3765456. Logistic regression was performed to investigate association between SNP within CD40 and CD226 and SLE. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among three SNPs. Logistic regression analysis showed that SLE risk was significantly higher in carriers of T allele of rs4810485 in CD40 gene than those with GG genotype (GT+ TT vs GG), adjusted OR (95 % CI) 1.84 (1.40–2.29). In addition, we also found SLE risk was also significantly higher in carriers of rs763361 T allele within CD226 gene than those with CC genotype (CT+ TT vs CC), adjusted OR (95 % CI) 1.89 (1.38–2.13). GMDR analysis suggested a potential gene–gene interaction between rs4810485 and rs763361. Overall, cross-validation consistency of the two-locus model was 10/10, and the testing accuracy was 62.17 %. We also found that subjects with GT or TT of rs4810485 and CT or TT of rs763361 genotype have the highest SLE risk, compared with subjects with GG of rs4810485 and CC of rs763361 genotype, and OR (95 % CI) was 2.14 (1.67–3.08), after covariates adjustment. Our results support an important association of rs4810485 in CD40 gene and rs763361 in CD226 gene polymorphism, combined effect of rs4810485 and rs763361 with increased risk of SLE.     

Association of peroxisome proliferator-activated receptor delta and additional gene–smoking interaction on cardiovascular disease

Aims: To investigate the impact of peroxisome proliferator–activator receptor delta (PPARD) gene polymorphism and additional gene–smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. Methods: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene–smoking interaction. Results: Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56–0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53–0.86). GMDR analysis suggested a potential gene–environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23–0.66). Conclusions: The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD.     

IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide polymorphisms

Objective: There has been significant interest in the association between asthma and the polymorphisms of IL-17A and IL-17F for a period of time. This work aims to present a clearer relationship between asthma and the polymorphisms of IL-17A and IL-17F. Method: Searches were performed in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between polymorphisms of IL-17A and IL-17F and asthma. Results: Nine studies comprising 3650 asthmatics and 3370 controls were included in this meta-analysis for all single nucleotide polymorphisms (SNPs) (2–6 per SNP). Our study examined the polymorphisms of IL-17F rs1889570 (C/T) (CC versus TT: OR?=?0.55, 95%CI?=?0.41–0.75; CT versus TT: OR?=?0.54, 95%CI?=?0.40–0.72; CC/CT versus TT: OR?=?0.55, 95%CI?=?0.42–0.72; CC versus CT/TT, OR?=?1.83, 95%CI?=?1.39–2.41), IL-17A rs4711998(A/G) (AA/AG versus GG: OR?=?0.67, 95%CI?=?0.46–0.98), and IL-17A rs3819024(A/G) (AA versus GG: OR?=?1.77, 95%CI?=?1.39–2.25) and found they were significantly related to the risk of asthma. Conclusion: Our systematic review showed that IL-17F rs1889570(C/T), IL-17A rs4711998(A/G) and IL-17A rs3819024(A/G) may be potential risk factors for asthma susceptibility.     

Association of AdipoQ single-nucleotide polymorphisms and smoking interaction with the risk of coronary heart disease in Chinese Han population

Aims: To investigate the impact of AdipoQ polymorphisms, and their additional interactions with smoking and drinking on coronary heart disease (CHD) risk based on Chinese population. Methods: Hardy?Weinberg equilibrium (HWE) was performed using SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) model was used to screen the best gene?gene and gene?environment interaction combinations. Logistic regression was performed to investigate association between four single-nucleotide polymorphisms (SNPs) and CHD and the interaction effect between rs1501299 and smoking. Results: Logistic analysis showed that CHD risks were higher in carriers with homozygous mutant of rs1501299 and rs2241766 than those with wild-type homozygotes, odds ratio (ORs) (95%CI) were 1.49 (1.19–1.95) and 1.71 (1.33–2.24), respectively, but CHD risks were lower in carriers with homozygous mutant of rs7649121 than those with wild-type homozygotes, OR (95%CI) was 0.72 (0.51–0.96). GMDR model indicated that there was a significant two-locus model (p = 0.0107) involving rs1501299 and current smoking, indicating a potential gene–environment interaction between rs1501299 and current smoking. Overall, the cross-validation consistency of this model was 9/10, and the testing accuracy was 60.11% (p = 0.0010). T-allele carriage had 42% prevalence, and one-quarter of them were current smokers. Smokers with rs1501299-GT or TT genotype have the highest CHD risk, compared to never-smokers with rs1501299-GG genotype, OR (95%CI) was 3.56 (1.91–5.42), after adjustment for gender, age, alcohol status, and body mass index. But we did not find any significant gene–gene and gene–drinking interaction combinations in GMDR models. Conclusions: Polymorphisms in rs1501299 and rs2241766, and their additional interactions between rs1501299 and smoking were associated with increased CHD risks: polymorphism in rs7649121 was associated with decreased CHD risks.     

PLA2G4A mutants modified protective effect of tea consumption against colorectal cancer

Purpose

The primary aim was to respectively evaluate PLA2G4A mutants modifying protective effect of tea consumption against colorectal cancer (CRC), colon and rectal cancer.

Methods

All participants were recruited from January 2006 to April 2008. The information about tea consumption was collected by a structured questionnaire. CRC patients were diagnosed based on histology. Four single-nuclear polymorphisms (SNPs) in PLA2G4A gene were selected. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC, colon and rectal cancer.

Results

Three hundred patients with CRC and 296 controls well-matched were used in the final analyses. The significant individual associations between four SNPs (rs6666834, rs10911933, rs4650708 and rs7526089) and CRC were not observed. However, their CTAC haplotype was significantly associated with the increased risk of CRC (OR?=?3.06; 95%CI?=?1.52–6.19), compared with TCAC haplotype. Drinking tea was correlated with a decreased risk of CRC after adjustment for covariates (OR?=?0.61; 95%CI?=?0.39–0.97). Meanwhile, compared with no-tea drinkers with TT/CT genotype of rs6666834, tea drinkers with TT/CT or CC had significant lower risk of CRC (OR?=?0.6, 95%CI?=?0.36–1.00 for TT/CT; 0.38, 0.19–0.74 for CC). The joint effects between the remaining three SNPs and drinking tea on CRC were observed as well. Similar findings were observed on colon and rectal cancers.

Conclusions

Tea consumption and haplotype of mutants in PLA2G4A gene were respectively associated with the risk of CRC. PLA2G4A mutants modified the protective effect of tea consumption against CRC, colon and rectal cancers in Chinese population.     

Association of Interleukin-6 Genetic Polymorphisms and Environment Factors Interactions with Coronary Artery Disease in a Chinese Han Population

Objectives: To investigate the influence of IL-6 single nucleotide polymorphisms (SNPs), additional gene-gene and gene-environment interactions on coronary artery disease (CAD) risk. Methods: A total of 751 participants (429 CAD patients and 322 controls) were recruited in this study. Logistic regression analysis was conducted to evaluate the association of IL-6 SNPs with CAD risk and generalized multifactor dimensionality reduction (GMDR) was performed to investigate the best interaction combinations for gene-gene and gene-environment interactions. Results: CAD risk is significantly higher in carriers of C allele of the rs1800795 polymorphism than those with GG genotype (CC + CG versus GG, adjusted OR (95%CI) = 2.07 (1.56–2.86), p < 0.001). GMDR analysis revealed rs1800795 was significantly interacted with tobacco smoking and alcohol drinking in two-locus model (p < 0.0010). Current smokers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.22 (2.45–3.94) and current drinkers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.17 (2.20–4.24). Conclusion: The C allele of rs1800795 within IL-6 gene promoter, rs1800795-tobacco smoking and rs1800795-alcohol drinking interaction were all associated with increased CAD risk.     

Lysosomal acid lipase gene single nucleotide polymorphism and pulmonary tuberculosis susceptibility

BackgroundThe factors that predispose to pulmonary tuberculosis (PTB) are not fully understood, However. Gene polymorphisms have been associated with PTB development.ObjectivesIn this study, we investigated the relationship between LIPA gene polymorphisms and a predisposition to pulmonary tuberculosis caused by Mycobacterium tuberculosis.MethodsA total of 202 cases of PTB and 218 healthy controls (HCS) were included in this study. Analyses were done under allelic, homozygous, and heterozygous, dominant, recessive models, and were used to calculate values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk. Genotyping was conducted using the real time polymerase chain reaction with high resolution melting curve analysis.ResultsWhen comparing PTB patients with healthy controls (HCS), significant associations with disease development were observed for both SNPs rs1051338 and rs7922269. Analysis was done based on models of genetic inheritance in man that is co-dominant, recessive and dominant models. Rs1051338, the heterozygous (AC vs. AA) P: 0.001, OR: 1.998, 95% CI: 1.312–3.042 and homozygous (CC vs. AA) P: < 0.001, OR: 4.078, 95% CI: 2.134–7.796 Co-dominant associated with increased risk for the disease. Under recessive (CC vs. AA + AC), P: 0.001, OR: 2.829: 95% CI: 1.543–5.185 and dominant model (AC + CC vs. AA) P: < 001, OR: 2.331, 95% CI: 1.564–3.474 the genotypes distribution increased the individual risk, plus its alleles distribution (P: < 0.001, OR: 2.004, 95% CI: 1.505–2.669). Considering SNP rs7922269 mutation significantly increased pulmonary tuberculosis risk as was observed in the homozygous GG vs. TT (P: 0.003, OR: 3.162, 95% CI: 1.431–6.989); heterozygous GT vs. TT (P: < 0.001, OR: 1.2.259, 95% CI: 1.503–3.394); dominant model (GT + GG vs. TT; P: < 0.001, OR: 2.061, 95% CI: 1.402–3.032) and the allele G (P: < 0.001, OR: 1.829, 95% CI:1.361–2.458), however no significant association was observed in the Recessive model (GG vs. TT + GT; P: 0.057, OR: 2.568, 95% CI: 0.965–4.432).ConclusionThe findings of our study strengthen the hypothesis that LIPA rs1051338 and rs7922269 polymorphism associated with increased risk for pulmonary Tb in a sample of northern Chinese population.     

Impact of interaction between CYP1A1 genetic polymorphisms and smoking on coronary artery disease in the Han of China

Aims: To investigate the association of CYP1A1 genotype and additional gene–smoking interaction with coronary artery disease (CAD) risk based on a Chinese case-control study. Methods: A total of 1862 participants (1134 men, 728 women) were selected, including 620 CAD patients and 1242 normal controls. Logistic regression was performed to investigate association of CYP1A1 genotype, gene–gene, and gene–smoking interaction with CAD. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best gene–gene and gene–smoking interaction combination, cross-validation consistency, the testing balanced accuracy, and the sign test, to assess if each selected interaction was calculated. Results: The carriers of homozygous mutant of rs4886605 polymorphism and heterozygous of rs4646903 are associated with increased CAD risk than those with wild-type homozygotes; OR (95% CI) was 1.98 (1.53–2.61) and 1.58 (1.24–1.96), respectively. The carriers of homozygous mutant of rs1048943 polymorphism is associated with decreased CAD risk than those with wild-type homozygotes, OR (95% CI) = 0.75 (0.60–0.93). GMDR model indicated a potential gene–gene interaction between rs4886605 and rs4646903 and a potential gene–smoking interaction between rs4886605 and smoking. Participants with rs4886605-CT or TT and rs4646903-TC or CC genotype have the highest CAD risk, compared to participants with rs4886605-CC and rs4646903-TT genotype; OR (95% CI) was 2.72 (2.03–3.61). In addition, we also found that smokers with rs4886605-CT or TT genotype have the highest CAD risk, compared to nonsmokers with rs4886605-CC genotype; OR (95% CI) was 3.07 (2.23–3.96). Conclusions: rs4886605 and rs4646903 are associated with increased CAD risk, but rs1048943 is associated with decreased CAD risk; we also found gene–gene interaction between rs4886605 and rs4646903 and gene–environment interaction between rs4886605 and smoking.     

TCF7L2 rs7903146 polymorphism is associated with gastric cancer: a case-control study in the Venezuelan population

AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms(SNPs) and gastric cancer risk in Venezuelan patients.METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinaltype gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene(rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined.RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model(OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele(CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer(dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model(OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer. CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.     

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility

Purpose: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. Methods: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. Results: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1–2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4–6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC–GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4–8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 – 2], P = 0.01). Conclusions: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC–GG combined genotype and C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.     

Association between PDE4D rs966221 polymorphism and risk of ischemic stroke: a systematic review and meta-analysis

PDE4D polymorphism (SNP83/rs966221) was reported to be associated with the susceptibility to ischemic stroke (IS), however, the results were inconclusive. An electronic search of Embase, PubMed, CNKI and Wan Fang Date was performed to identify relevant studies published throughout April 2017. A total of 26 studies were enrolled in the analysis. No significant association between the rs9662221 polymorphism and IS was observed in the overall analysis. Nevertheless, in the subgroup analysis, our results showed a significant association between the SNP83 polymorphism and IS in CC+ CT vs. TT (OR?=?1.19, 95% CI: 1.02–1.38), CT vs.TT (OR?=?1.14, 95% CI: 1.01–1.29) and C vs. T (OR?=?1.25, 95% CI: 1.06–1.48) in Asian population. But we did not found any association in CC vs. CT?+?TT (OR?=?1.2, 95% CI: 0.9–1.61) and CC vs. TT (OR?=?1.26, 95% CI: 0.91–1.75) in the Asian populations. Meantime, no significant correlations were observed under the five genetic model in Caucasian population (p?>?0.05). In conclusion, our meta-analysis demonstrated that the SNP83 polymorphism in the PDE4D gene might contribute to IS susceptibility especially in Asian populations. Whereas the relationship of the polymorphism to the disease in Caucasian population was still in controversial. In future, additional well designed studies with larger sample sizes are still required to further elucidate this association.     

细胞色素氧化酶基因CYP1A2多态性与新疆汉族和维吾尔族人群冠心病的相关性

目的 探讨新疆地区维吾尔（维）族人群、汉族人群细胞色素氧化酶基因CYP1A2（cytochrome c oxidase P1A2）多态性与冠心病的关联性。 方法 我们采用两项独立的病例对照研究∶汉族人群389例冠心病患者(病例组）和411名健康体检者（对照组）;维族人群293冠心病患者（病例组）和408名健康体检者（对照组）。通过实时PCR对CYP1A2基因单核苷酸多态性（SNPs）rs2069522和rs2472304进行基因分型。 结果 仅在汉族人群中,SNP1 (rs2069522)基因型的分布在冠心病组和对照组之间差异均有统计学意义(P < 0.05)。而维族人群中未见显著差异。新疆汉族病例组SNP1 (rs2069522)显性模型(CC vs CT + TT)基因型频率显著高于对照组。调整混杂因素后logistic回归分析表明,新疆汉族人群CC基因型患冠心病的风险显著高于CT + TT基因型者(总体:OR = 1.982,95%CI: 1.174～3.236, P < 0.01;男性: OR = 2.671,95%CI: 1.548～4.314, P < 0.01)。 结论 新疆汉族人群CYP1A2基因中rs2069522的位点与冠心病相关。CC基因型可能是新疆汉族人群而非维吾尔族人群发生冠心病的独立危险因素。     

The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population

Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase pathway of arachidonic acids metabolism for the pathogenesis of essential hypertension (EH). The present study was designed to investigate whether common single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8 (rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are associated with susceptibility to EH in Russian population. A total of 816 unrelated Russian individuals comprising 425 EH patients and 391 normotensive controls were included into the study. Genotyping of SNPs was performed using the MassARRAY 4 system. SNP rs7909236 of CYP2C8 was significantly associated with increased risk of EH (OR adjusted for sex and age was 2.99 95% CI 1.39-6.44, P = 0.005). SNPs rs1934953 CYP2C8 and rs4244285 of CYP2C19 showed association with EH risk but at a borderline statistical significance (P ≤ 0.04). Combination of genotypes CYP2C8 rs7909236 TT and CYP2C19 rs4244285 GG was associated with increased EH risk (OR 3.34 95%CI 1.48-7.51, P = 0.004). Genotype–phenotype correlation analysis showed that the levels of CYP2C8 mRNA were significantly correlated with SNP rs7909236 (P = 0.01). in silico functional prediction analysis revealed the functionality of majority of investigated SNPs. Thus, genes of CYP2C subfamily are important genetic determinants of susceptibility to essential hypertension in Russians.     

恩施土家族人群eNOS rs1799983基因多态性和肥胖在原发性高血压中的交互作用

目的 探讨恩施土家族人群内皮型一氧化氮合酶(eNOS)rs1799983多态性与原发性高血压(EH)关联性及其与肥胖交互作用。方法 采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析127例EH患者和127名正常对照eNOS rs1799983基因型。非条件Logistic分析各基因型与发病中易感性关系以及与肥胖的交互作用。结果 携带C(CC/CT)基因个体患病风险较非C基因携带者(TT)风险明显增加1.35倍(OR=1.35,95%CI: 1.22,2.56,P<0.01;校正OR=1.61,95%CI: 1.21,3.01,P<0.01);非条件Logistic分析表明携带CC/CT基因型肥胖个体EH罹患风险是携带TT基因非肥胖个体的3.39倍(OR=3.39,95%CI:2.66,5.36,P=0.000)(RERI=1.94,95%CI:1.41,2.77;API=0.59,95%CI:0.33,0.84;S=1.46,95%CI:1.37,2.66)。结论 eNOS rs1799983多态性增加恩施土家族个体原发性高血压罹患风险,且与肥胖存在原发性高血压发病中存在协同效应。     

Genetic polymorphism of IL28B in hepatitis C‐infected haemophilia patients in Israel

Single‐nucleotide polymorphisms (SNPs) near the IL28B gene were identified as major predictors of treatment response (sustained virologic response – SVR) and spontaneous clearance of HCV. Haemophilia patients have the highest prevalence of HCV, and are a unique target for genetic studies. The Israeli population is ethnically heterogeneous; therefore, genetic variability is anticipated. To determine the IL28B haplotypes in HCV‐infected haemophilia patients and association with SVR and spontaneous viral clearance. IL28B polymorphism at SNPs rs12979860 and rs8099917 was determined in sera obtained from 130 HCV‐infected haemophilia patients. The frequency of the various haplotypes was analysed according to treatment response, spontaneous HCV clearance, viral load and degree of fibrosis. The CC haplotype at SNP rs12979860 was found in 31% of patients, whereas the TT genotype at SNP rs8099917 was detected in 57% of cases. SVR was achieved in 70% of patients carrying the CC haplotype (P = 0.0196 vs. CT/TT), and 50% of the TT genotype at SNP rs8099917 (P = 0.0227 vs. TG/GG). Thirty‐five percent of patients carrying the CC haplotype and 26% with the TT genotype at SNP rs8099917 showed spontaneous clearance of HCV infection (P = 0.00262 vs. CT/TT; and P = 0.00371 vs. TG/GG respectively). The C‐allele frequency was exceptionally high (71%) in immigrants from the Asian republics of Russia. In HCV‐infected haemophilia patients, SVR was more commonly achieved among patients who had the CC ( rs12979860 ) or TT ( rs8099917 ) genotype. Likewise, patients who possess harbour the CC or TT genotypes were more likely to clear HCV infection spontaneously. A unique distribution of the CC genotype was observed in some ethnic groups.     

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086–7.090, p?=?0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727–6.661, p?=?0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379–1.472, p?=?0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544–1.956, p?=?0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.     

Functional polymorphism rs189037 in the promoter region of ATM gene is associated with angiographically characterized coronary stenosis

Objectives

To evaluate the association between the single nucleotide polymorphism rs189037 of the ataxia-telangiectasia mutated (ATM) gene and angiographically characterized coronary stenosis as well as the molecular basis of this association.

Results

In 562 patients treated at the Department of Cardiology, West China Hospital, a significant association was found between polymorphism rs189037 and angiographically characterized coronary stenosis. For the T versus C allele, the adjusted OR was 0.79 (95%CI 0.67–0.92, P = 0.003), using the allele frequency model; for TT versus CT/CC, the adjusted OR was 0.36 (95%CI 0.21–0.59, P = 0.00006), using the recessive model; and for TT/CT versus CC, the adjusted OR was 0.54 (95%CI 0.29–1.02, P = 0.06), using the dominant model. An antagonism was found between polymorphism rs189037 and diabetes mellitus (P = 0.003). In coronary artery disease (CAD) patients, the TT genotype of rs189037 was associated with higher ATM mRNA expression (F = 4.23, P = 0.02) in peripheral mononuclear cells than the CC or CT genotypes.

Conclusion

Polymorphism rs189037 may influence the expression of ATM mRNA in CAD patients. It is also associated with the degree of coronary stenosis. Moderately low expression of the ATM gene may be associated with the development of coronary atherosclerosis.     

IL28B genetic variants and gender are associated with spontaneous clearance of hepatitis C virus infection

Summary. Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus (HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV‐infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY^® SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07–112.50), 14.88 (2.02–109.72), 7.92 (1.88–33.32) and 2.32 (1.22–4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men [56/213 (26.3%) vs 24/163 (14.6%), P = 0.007], and this was true even after stratification for IL28B genotypes with OR of 1.9–2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.     

Association of XPG rs2094258 polymorphism with gastric cancer prognosis

BACKGROUND The xeroderma pigmentosum group G(XPG)gene at chromosome 13q33 consists of 15 exons,which may be related to the occurrence and development of gastric cancer(GC).AIM To examine the association of several common single nucleotide polymorphisms(SNPs)of the XPG gene with GC risk and survival.METHODS Five SNPs of XPG(rs2094258,rs751402,rs873601,rs2296147,and rs1047768)were genotyped by PCR restriction fragment length polymorphism in 956 histologically confirmed GC cases and 1012 controls in North China.GC patients were followed for survival status and,if deceased,cause of death.Logistic regression and Cox regression were used for analysing associations of XPG SNPs with risk of GC and prognosis,respectively.For rs2094258,heterozygous model(CT vs CC),homozygous model(TT vs CC),recessive model(TT vs CT+CC),and dominant model(TT+CT vs CC)were analyzed.RESULTS None of the examined loci were statistically associated with GC risk,although rs2296147 was marginally associated with GC risk(P=0.050).GC patients with the rs2094258 CT+CC genotype showed worse survival than those with the TT genotype(log-rank test,P=0.028),and patients with the CC genotype had a tendency of unfavourable prognosis compared with those with the TT+CT genotype(log-rank test,P=0.039).The increase in C alleles of rs2094258[hazard ratio(HR)=1.19,95%confidence interval(CI):1.02-1.45,P=0.037]were associated with the long-term survival of GC cases.Other risk factors for survival included tumor differentiation(HR=4.51,95%CI:1.99-8.23,P<0.001),lymphovascular invasion(HR=1.97,95%CI:1.44-3.01,P<0.001),and use of chemotherapy(HR=0.81,95%CI:0.63-0.98,P=0.041).CONCLUSION The XPG rs2094258 polymorphism may be associated with overall survival in GC patients.