Associations of polymorphisms in TXNIP and gene-environment interactions with the risk of coronary artery disease in a Chinese Han population.
Associations of polymorphisms in TXNIP and gene-environment interactions with the risk of coronary artery disease in a Chinese Han population.
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DOI：
10.1111/jcmm.12929
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发表时间：
2016-12
影响因子：
5.3
通讯作者：
Zheng F
中科院分区：
文献类型：
--
作者：
Wang XB;Han YD;Zhang S;Cui NH;Liu ZJ;Huang ZL;Li C;Zheng F
硫氧还蛋白相互作用蛋白（TXNIP）基因的单核苷酸多态性（snp）可能调节TXNIP的表达，从而增加冠心病（CAD）的风险。在一项共有1818名CAD患者和1963名对照的两阶段病例对照研究中，我们在TXNIP中对三个snp进行了基因分型，发现在显性模型下，snp rs7212（优势比(OR) = 1.26, P = 0.001）和rs7211 （OR = 1.23, P = 0.005）的变异基因型与CAD风险增加显著相关。在单倍型分析中，与参考单倍型相比，单倍型“G‐T”患CAD的风险增加了1.22倍（P = 0.003）。我们还观察到snp rs7212和rs7211对冠心病风险和冠状动脉粥样硬化严重程度的累积效应。此外，SNP rs7212变异基因型、吸烟习惯、饮酒习惯和2型糖尿病史之间的基因-环境相互作用与冠心病风险增加3.70倍相关（P < 0.001）。随后的基因型-表型相关分析进一步观察到SNP rs7212对TXNIP mRNA表达、血浆TXNIP和丙二醛水平的显著影响。综上所述，我们的数据表明TXNIP snp可能通过调节TXNIP表达和基因-环境相互作用的可能机制单独和累积地影响CAD风险。
Single nucleotide polymorphisms (SNPs) in thioredoxin‐interacting protein (TXNIP) gene may modulate TXNIP expression, then increase the risk of coronary artery disease (CAD). In a two‐stage case–control study with a total of 1818 CAD patients and 1963 controls, we genotyped three SNPs in TXNIP and found that the variant genotypes of SNPs rs7212 [odds ratio (OR) = 1.26, P = 0.001] and rs7211 (OR = 1.23, P = 0.005) were significantly associated with increased CAD risk under a dominant model. In haplotype analyses, compared with the reference haplotype, haplotype ‘G‐T’ had a 1.22‐fold increased risk of CAD (P = 0.003). We also observed the cumulative effects of SNPs rs7212 and rs7211 on CAD risk and the severity of coronary atherosclerosis. Moreover, the gene–environment interactions among the variant genotypes of SNP rs7212, smoking habit, alcohol drinking habit and history of type 2 diabetes were associated with a 3.70‐fold increased risk of CAD (P < 0.001). Subsequent genotype‐phenotype correlation analyses further observed the significant effects of SNP rs7212 on TXNIP mRNA expression, plasma TXNIP and malondialdehyde levels. Taken together, our data suggest that TXNIP SNPs may individually and cumulatively affect CAD risk through a possible mechanism for regulating TXNIP expression and gene–environment interactions.
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