BACKGROUND Accumulating evidence has shown that type 2 diabetes (T2D) and coronary artery disease (CAD) may stem from a 'common soil'. The aim of our study was to examine the association between genetic predisposition to T2D and the risk of severe CAD among patients with acute coronary syndromes (ACS) undergoing angiography. METHODS The current case-control study included 1414 ACS patients with at least one major epicardial vessel stenosis > 50% enrolled in the ACS Genetic Study. The severity of CAD was quantified by the number of coronary arteries involved. Genetic risk score (GRS) was calculated using 41 common variants that robustly associated with increased risk of T2D in East Asians. Logistic regression models were used to estimate the association between GRS and the severity of CAD. RESULTS In the age-, sex- and BMI-adjusted model, each additional risk allele was associated with a 6% increased risk of multi-vessel disease (OR = 1.06, 95% CI 1.02-1.09). The OR was 1.43 (95% CI 1.08-1.89) for the risk of severe CAD when comparing the extreme tertiles of T2D-GRS. The association was not reduced after further adjustment for conventional cardiovascular risk factors. Additional adjustment for T2D status in our regression model attenuated the association by approximately one quarter. In subgroup analysis, the strengths of the associations between GRS and the severity of CAD were broadly similar in terms of baseline demographic information and disease characteristics. CONCLUSIONS Our data indicated that genetic predisposition to T2D is associated with elevated risk of severe CAD. This association revealed a possible causal relationship and is partially mediated through diabetic status.

中文翻译：

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2型糖尿病的遗传易感性与急性冠脉综合征患者的冠状动脉疾病严重程度有关。

背景技术越来越多的证据表明2型糖尿病（T2D）和冠状动脉疾病（CAD）可能源自“普通土壤”。我们研究的目的是检查接受血管造影的急性冠脉综合征（ACS）患者的T2D遗传易感性与严重CAD风险之间的关系。方法目前的病例对照研究包括1414例ACS遗传研究中至少有1个主要心外膜血管狭窄> 50％的ACS患者。CAD的严重程度通过涉及的冠状动脉数量进行量化。遗传风险评分（GRS）是使用41种常见变体计算得出的，这些变体与东亚T2D风险增加紧密相关。Logistic回归模型用于估计GRS和CAD严重程度之间的关联。结果在这个时代，性别和BMI调整后的模型，每增加一个风险等位基因与多支血管疾病风险增加6％相关（OR = 1.06，95％CI 1.02-1.09）。比较T2D-GRS的三分位数时，发生严重CAD的风险OR为1.43（95％CI 1.08-1.89）。进一步调整常规心血管危险因素后，相关性并未降低。在我们的回归模型中对T2D状态进行额外的调整会使关联降低约四分之一。在亚组分析中，就基线人口统计信息和疾病特征而言，GRS与CAD严重程度之间的关联强度大致相似。结论我们的数据表明，T2D的遗传易感性与严重CAD的风险升高有关。