Open AccessAssociations of polymorphisms in TXNIP and gene–environment interactions with the risk of coronary artery disease in a Chinese Han population
Author(s) -
Wang Xuebin,
Han Yadi,
Zhang Shuai,
Cui Ninghua,
Liu Zejin,
Huang Zhuliang,
Li Cong,
Zheng Fang
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12929
Subject(s) - txnip , single nucleotide polymorphism , haplotype , snp , genotype , coronary artery disease , odds ratio , biology , medicine , genetics , gene , thioredoxin
Single nucleotide polymorphisms ( SNP s) 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 SNP s in TXNIP and found that the variant genotypes of SNP s 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 SNP s 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 SNP s may individually and cumulatively affect CAD risk through a possible mechanism for regulating TXNIP expression and gene–environment interactions.