Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
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DOI：
10.1371/journal.pone.0017978
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发表时间：
2011-03-15
期刊：
影响因子：
3.7
通讯作者：
Drexel H
中科院分区：
文献类型：
--
作者：
Muendlein A;Saely CH;Geller-Rhomberg S;Sonderegger G;Rein P;Winder T;Beer S;Vonbank A;Drexel H
冠状动脉疾病（CAD）与2型糖尿病（T2 DM）有共同的危险因素。转录因子7样2（TCF 7 L2）基因的变异，特别是rs7903146，增加了T2 DM的风险。TCF 7 L2基因座的遗传变异与冠状动脉粥样硬化之间的潜在联系尚不确定。因此，我们研究了糖尿病和非糖尿病患者TCF 7 L2多态性与血管造影确定的CAD之间的关系。我们在一项横断面研究中对TCF 7 L2变异体rs7903146、rs 12255372和rs 11196205进行了基因分型，该研究包括1,650例连续接受冠状动脉造影的患者，以评估确诊或疑似稳定型CAD。在冠状动脉狭窄≥ 50%的情况下诊断为显著CAD。总研究队列中的变异rs7903146与显著CAD显著相关（校正的相加OR = 1.29 [1.09-1.53]; p = 0.003）。 这种关联在T2 DM患者中很强且显著（n = 393; OR = 1.91 [1.32-2.75]; p = 0.001），但在非糖尿病受试者中不显著（OR = 1.09 [0.90-1.33]; p = 0.370）。 T2 DM的相互作用风险等位基因是显著的（pinteraction = 0.002），表明T2 DM患者中的多态性对CAD的影响显著强于非糖尿病受试者。 TCF 7 L2多态性rs 12255372和rs 11196205也与糖尿病患者的CAD显著相关（分别为校正的相加OR = 1.90 [1.31-2.74]; p = 0.001和OR = 1.75 [1.22-2.50]; p = 0.002）。 此外，单倍型分析表明，包括所有研究变体的罕见等位基因在内的单倍型与整个队列以及糖尿病受试者中的CAD显著相关（分别为OR= 1.22 [1.04-1.43]; p = 0.013和OR = 1.67 [1.19-2.22]; p =0.003）。 这些结果表明，TCF 7 L2变体rs7903146、rs 12255372和rs 11196205与血管造影诊断的CAD显著相关，特别是在T2 DM患者中。因此，TCF 7 L2似乎是糖尿病和动脉粥样硬化之间的遗传联系。
Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary atherosclerosis are uncertain. We therefore investigated the association between TCF7L2 polymorphisms and angiographically determined CAD in diabetic and non-diabetic patients. We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses ≥50%. Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive OR = 1.29 [1.09–1.53]; p = 0.003). This association was strong and significant in T2DM patients (n = 393; OR = 1.91 [1.32–2.75]; p = 0.001) but not in non-diabetic subjects (OR = 1.09 [0.90–1.33]; p = 0.370). The interaction risk allele by T2DM was significant (pinteraction = 0.002), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rs12255372 and rs11196205 were also significantly associated with CAD in diabetic patients (adjusted additive OR = 1.90 [1.31–2.74]; p = 0.001 and OR = 1.75 [1.22–2.50]; p = 0.002, respectively). Further, haplotype analysis demonstrated that haplotypes including the rare alleles of all investigated variants were significantly associated with CAD in the whole cohort as well as in diabetic subjects (OR = 1.22 [1.04–1.43]; p = 0.013 and OR = 1.67 [1.19–2.22]; p = 0.003, respectively). These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM. TCF7L2 therefore appears as a genetic link between diabetes and atherosclerosis.
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