Genetic Markers of CHD in Type 2 Diabetes

摘要 冠心病(CHD)是发病率和死亡率的主要原因，在2型中尤为常见。 糖尿病。遗传因素和环境因素共同决定着冠心病的发生发展。最新全基因组 协会(GWA)的研究已经在普通人群中发现了几种CHD的遗传变异。现在是时候了 优先开展糖尿病患者冠心病的GWA研究。此外，更好地了解 冠心病的病因学需要仔细研究中间生化变化和基因突变。 环境相互作用。护士健康研究(NHS)和卫生专业人员随访研究(HPFS) 是具有良好特征的队列，其存储的DNA样本和详细的生活方式信息可用。 通过单独的NIH拨款，我们将在以下时间完成GWA扫描(Affymetrix SNP阵列6.0；约100万个SNP 截至2008年7月，来自NHS/HPFS的3,000例糖尿病患者(950例冠心病/2,050例非冠心病)。我们建议对GWA进行分析 在两项糖尿病冠心病病例对照研究中复制前1200-1400个SNP与冠心病风险的关系 患者：乔斯林心脏研究(N=1400)和哥斯达黎加研究(N=890)。我们还将评估这些协会 与CHD的生化危险因素，并检查基因-环境的相互作用。GWA扫描， 生化标记物测量，并收集有关生活方式因素的详细信息 单独授予。因此，拟议的项目将具有极高的成本效益。我们已经集合好了 一群经验丰富、敬业的合作者，他们在遗传流行病学、统计学 遗传学、生物信息学、心血管疾病、糖尿病和营养学。我们相信史无前例的 这个项目中可用的资源将提供一个独特的机会来确定过度风险的遗传因素。 糖尿病患者发生冠心病的风险。

Abstract Coronary heart disease (CHD) is a leading cause of morbidity and mortality and particularly frequent in type 2 diabetes. Both genetic and environmental factors determine the development of CHD. Recent genome-wide association (GWA) studies have identified several genetic variants for CHD in the general population. It is now a high priority to conduct GWA study for CHD in diabetic patients. In addition, a better understanding of the etiology of CHD requires a careful investigation of intermediate biochemical changes and gene- environment interactions. The Nurses' Health Study (NHS) and Health Professionals' Follow-up Study (HPFS) are well-characterized cohorts whose stored DNA sample and detailed lifestyle information are available. Through a separate NIH grant, we will complete a GWA scan (Affymetrix SNP Array 6.0; ~1 million SNPs) in 3,000 diabetic cases (950 CHD/2,050 non-CHD) from NHS/HPFS by July, 2008. We propose to analyze GWA data with the CHD risk and replicate the top 1200-1400 SNPs in two CHD case-control studies of diabetic patients: Joslin Heart Study (N=1,400) and Costa Rica study (N=890). We will also assess the associations with biochemical risk factors for CHD and examine the gene-environment interactions. The GWA scan, biochemical marker measurement, and collection of detailed information on lifestyle factors have been separately granted. Therefore the proposed project will be extremely cost-efficient. We have assembled a solid group of experienced and committed collaborators with expertise in genetic epidemiology, statistical genetics, bioinformatics, cardiovascular disease, diabetes, and nutrition. We believe that the unprecedented resources available in this project will provide a unique opportunity to identify genetic factors for excessive risk of CHD in diabetic patients.