Modification of PM-Mediated Arrhythmogenesis in Populations

描述（由申请人提供）：拟议的研究检查了对常见遗传变异引起的颗粒物（PM）空气污染致突变效应的敏感性。它的基本原理来自于PM空气污染的环境浓度与急性冠心病（CHD）事件之间的既定但异质的关联，这是一种广泛但对公共健康知之甚少的威胁。它的重点是休息，标准的12导联心电图测量，已被链接到环境PM浓度一方面，另一方面，急性CHD事件。它将最佳地利用来自妇女健康倡议临床试验（WHI CT）的基因组，环境和心电图数据，SNP健康协会资源项目（SHARe，NHLBI-PB-2006-091），WHI心律失常发生的环境流行病学（5-R 01-ES 012238）、社区动脉粥样硬化风险（ARIC）研究和使用基因组学和流行病学的人群结构（PAGE）联盟。具体而言，它将检查1987年至2004年期间评估的七个不同亚群的心率变异性，心室复极，心肌缺血和心室异位的措施。这七个亚群包括：（1）5148名黑人女性，（2）2002名西班牙裔女性，（3）1507名白色女性，在WHI CT中有心室异位，1507名无心室异位;在ARIC研究中，（4）2615名黑人女性，（5）5989名白色女性，（6）1621名黑人男性，（7）5369名白色男性。亚群1-7将用于独立鉴定在Affytek 6.0阵列上基因分型的约106个单核苷酸多态性（SNP）与在地理编码的参与者地址空间内插的每日平均环境PM浓度之间的基因-环境相互作用。还将研究SNP的主要影响。壁内共同资助的分析将具有良好的把握度，并适当调整多重比较。预期的发现将为检查跨种族和性别的关联的一致性提供基础。总的来说，他们将在美国环境保护署（EPA）1-10区的25，758名均匀特征良好的参与者的种族和地理代表性人群中，促进对PM介导的乳腺癌发生的遗传易感性和病理生理机制的理解。这一进展将深入了解PM引起的ECG异常的比例，这些异常可以通过建立和遵守更严格的国家环境空气质量标准来减少。 公共卫生相关性：这项拟议的研究将有效地促进对PM介导的乳腺癌发生的遗传易感性和病理生理机制的理解，该研究在美国环境保护署（EPA）1-10区的25，758名均匀特征良好的参与者中具有种族和地理代表性。其理论基础来自环境颗粒物空气污染水平与急性冠心病事件之间已建立但不均匀的关联，这是一种广泛但对公共健康知之甚少的威胁。

DESCRIPTION (provided by applicant): The proposed study examines susceptibility to the arrhythmogenic effects of particulate matter (PM) air pollution contributed by common genetic variation. Its rationale derives from the established, but heterogeneous association between ambient concentrations of PM air pollution and acute coronary heart disease (CHD) events, a widespread, but poorly understood threat to public health. Its focus is on resting, standard twelve-lead ECG measures that have been linked to ambient PM concentrations on the one hand, and to acute CHD events on the other. It will optimally leverage the genomic, environmental and electrocardiographic data from the Women's Health Initiative clinical trial (WHI CT), The SNP Health Association Resource project (SHARe, NHLBI-PB-2006-091), The Environmental Epidemiology of Arrhythmogenesis in WHI (5-R01-ES012238), the Atherosclerosis Risk in Communities (ARIC) study and the Population Architecture using Genomics and Epidemiology (PAGE) consortium. Specifically, it will examine measures of heart rate variability, ventricular repolarization, myocardial ischemia and ventricular ectopy within seven distinct subpopulations evaluated between 1987 and 2004. The seven subpopulations include: (1) 5148 black women, (2) 2002 Hispanic women, and (3) 1507 white women with and 1507 without ventricular ectopy in the WHI CT; and in the ARIC study, (4) 2615 black women, (5) 5989 white women, (6) 1621 black men, and (7) 5369 white men. Subpopulations 1-7 will be used to independently identify gene-by-environment interactions between approximately 106 single nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array and daily mean ambient PM concentrations spatially interpolated at geocoded participant addresses. SNP main effects will also be investigated. The intramurally co-funded analyses will be well-powered and appropriately adjusted for multiple comparisons. Anticipated findings will provide a foundation for examining the consistency of associations across race and gender. Collectively, they will advance understanding of genetic susceptibility to and the pathophysiological mechanisms underlying PM-mediated arrhythmogenesis in an ethnically and geographically representative population of 25,758 uniformly well-characterized participants living in U.S. Environmental Protection Agency (EPA) Regions 1-10. The advance will provide insight into the proportion of PM-attributable ECG abnormalities that could be reduced by establishing and complying with stricter National Ambient Air Quality Standards. PUBLIC HEALTH RELEVANCE: The proposed study will efficiently advance understanding of genetic susceptibility to and the pathophysiological mechanisms underlying PM-mediated arrhythmogenesis in an ethnically and geographically representative population of 25,758 uniformly well-characterized participants living in U.S. Environmental Protection Agency (EPA) Regions 1-10. Its rationale derives from the established, but heterogeneous association between ambient levels of particulate matter air pollution and acute coronary heart disease events, a widespread, but poorly understood threat to public health.