Genetics Markers of CHD Risk in Men and Women

男性和女性冠心病风险的遗传学标志

• 批准号: 6821665
• 负责人: RICHARD P DONAHUE
• 金额: $ 40.41万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6821665
• 关键词: cardiovascular disorder risk; clinical research; gender difference; genetic markers; genetic susceptibility; human genetic material tag; human middle age (35-64); human old age (65+); human tissue; inflammation; myocardial infarction; postmenopause; selectins; single nucleotide polymorphism

DESCRIPTION (provided by applicant): We propose to determine whether the variability in several genes that influence inflammation and endothelial dysfunction is related to the odds of MI among 700 men and 229 postmenopausal women from the Western New York Health Study. We will examine the following specific aims. 1) We hypothesize that cases of acute MI will have a higher frequency of specific haplotypes at the C-reactive protein locus composed of alleles associated with higher levels of CRP production (-732G/A), 1059G/C, and +1444C/T) than matched controls. MI cases will have a greater frequency of haplotypes composed of alleles associated with higher levels of IL-6 production (-597G/A, -572G/C, and -174G/C) than controls, and a lower frequency of specific !haplotypes in the IL1A/IL1 BILL1RN gene region; 2) cases will have a higher frequency of alleles and haplotypes for specific functional polymorphisms of the E-selectin gene ($128R and G98T) than controls; 3) to utilize DNA pooling strategy for rapid screening of large numbers of single nucleotide polymorphisms (SNPs) in 29 candidate genes in relevant biological pathways and test selected loci for association with risk of acute MI; 4) for those loci with evidence of association, to identify haplotype tagging SNPs (htSNPs) that capture the variation at each locus and test for association between these SNPs and haplotypes and risk of MI. Secondary aims will a) explore the above associations among men with premature MI (55 years of age or less) and b) explore gene- gene and gene- environment interactions. MI case subjects were identified from hospital record review in Erie and Niagara counties (95% of all eligible cases, ICD9 410-410.9) an average of 4 months post MI. They were interviewed and examined in 1996-2001. Control subjects were randomly selected from the same counties (59.5% response rate) and had a contemporaneous clinical exam. Controls will be individually matched to cases by age, sex, and ethnicity. This innovative and cost efficient method may yield new insights into the genetic risks underlying acute MI.

描述（由申请人提供）：我们建议在来自西纽约健康研究的700名男性和229名绝经后女性中确定影响炎症和内皮功能障碍的几种基因的变异性是否与MI的几率相关。我们将研究以下具体目标。1)我们假设急性心肌梗死病例在C反应蛋白基因座上的特异性单倍型频率较高，这些单倍型由与较高水平CRP产生相关的等位基因（-732G/A、1059 G/C和+1444C/T）组成。与对照组相比，MI病例具有更高频率的由与更高水平的IL-6产生（-597G/A、-572G/C和-174G/C）相关的等位基因组成的单倍型，以及更低频率的特异性IL-6产生。IL 1A/IL 1 BILL 1 RN基因区域的单倍型; 2）病例将具有更高频率的E-选择素基因特异性功能多态性的等位基因和单倍型（$128R和G98 T）高于对照组; 3）利用DNA池策略快速筛查大量单核苷酸多态性（SNP）在相关生物学途径中的29个候选基因中，并测试与急性MI风险相关的选定基因座; 4）对于那些有关联证据的位点，识别单倍型标记SNP（htSNP）捕捉每个位点的变异，并检测这些SNP与单倍型和MI风险之间的关联。次要目的是a）探索早发MI（55岁或以下）男性中的上述相关性，和B）探索基因-基因和基因-环境相互作用。MI病例受试者是在MI后平均4个月通过伊利和尼亚加拉县的医院记录审查确定的（所有合格病例的95%，ICD 9 410-410.9）。他们在1996-2001年接受了面谈和检查。对照组受试者从相同的县（59.5%的应答率）随机选择，并进行同期临床检查。对照组将根据年龄、性别和种族与病例进行单独匹配。这种创新和成本效益的方法可能会产生新的见解急性心肌梗死的遗传风险。