Genetic Variants of Diabetes Risk and Incident Cardiovascular Events in Chronic Coronary Artery Disease

ObjectiveTo determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence.
MethodsFrom the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve.
ResultsGenetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610).
ConclusionsCombined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease.
Clinical Trial Registration InformationMedicine, Angioplasty, or Surgery Study (MASS II). Unique identifier: ISRCTN66068876 URL.

研究目的：明确糖尿病遗传风险变异相关信息是否与心血管事件发生率存在关联。
研究方法：从约30个已被证实与糖尿病相关的基因中，我们针对多支血管冠状动脉疾病患者的随机对照研究——MASS-II研究的425名受试者，对与2型糖尿病关联最密切的10个基因位点的单核苷酸多态性（single-nucleotide polymorphisms）进行了基因分型。我们以糖尿病风险等位基因数量来评估综合遗传信息。通过Kaplan-Meier曲线比较与Cox比例风险模型（Cox Hazard Models），分析遗传模型对主要心血管事件发生率的预测效能；并通过计算受试者工作特征曲线下面积（area under the ROC curve, AUC），评估模型对心血管事件的区分能力。
研究结果：即使在校正了包括空腹血糖在内的潜在混杂因素后，遗传信息仍可预测非糖尿病受试者的5年主要心血管事件发生率与全因死亡率。高遗传风险的非糖尿病受试者的事件发生率与糖尿病受试者相近（累积风险分别为33.0%与糖尿病受试者的35.1%）。将综合遗传信息加入临床预测模型后，心血管事件发生率预测的AUC值显著提升（AUC=0.641 vs 0.610）。
研究结论：在合并冠状动脉疾病的非糖尿病个体中，糖尿病风险遗传变异的综合信息与主要心血管事件发生率（包括全因死亡率）存在关联。
临床试验注册信息：医学、血管成形术与外科研究（Medicine, Angioplasty, or Surgery Study, MASS II）。唯一标识符：ISRCTN66068876，相关网址（原文本未提供完整URL）。