Modification of PM-Mediated Arrhythmogenesis in Populations

PM 介导的人群心律失常发生的改变

• 批准号: 7984809
• 负责人: Eric A. Whitsel
• 金额: $ 76.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7984809
• 关键词: Acute; Address; Air; Air Pollution; Architecture; Arrhythmia; Atherosclerosis; Awareness; Behavioral; Candidate Disease Gene; Cardiovascular system; Clinical Trials; Communities; Coronary heart disease; Data; Electrocardiogram; Environmental Epidemiology; Environmental Health; Epidemiologic Studies; Epidemiologist; Epidemiology; Event; Exposure to; Foundations; Funding; Gender; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genomics; Genotype; Hand; Health; Hemostatic Agents; Hispanics; Inflammatory; Life; Link; Measures; Mediating; Metabolic; Metric; Modification; Morbidity - disease rate; Myocardial Ischemia; Nature; Participant; Particulate Matter; Population; Population Heterogeneity; Population Study; Predisposition; Public Health; Quality Control; Race; Resources; Rest; Risk; Scientist; Single Nucleotide Polymorphism; United States Environmental Protection Agency; Ventricular; Woman; Women' s Health; base; gene environment interaction; genetic variant; genome wide association study; heart rate variability; insight; men; mortality; novel; public health relevance; socioeconomics

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.

描述（由申请人提供）：拟议的研究检查了常见遗传变异对颗粒物（PM）空气污染造成的心律失常影响的敏感性。其基本原理源自于环境中 PM 空气污染浓度与急性冠心病 (CHD) 事件之间已确定但存在异质性的关联，而急性冠心病 (CHD) 是一种广泛存在但对公众健康构成的威胁，但人们对此知之甚少。其重点是静息、标准十二导联心电图测量，这些测量一方面与环境 PM 浓度有关，另一方面与急性冠心病事件有关。它将最佳地利用来自妇女健康倡议临床试验 (WHI CT)、SNP 健康协会资源项目 (SHARe、NHLBI-PB-2006-091)、WHI 中心律失常发生的环境流行病学 (5 -R01-ES012238），社区动脉粥样硬化风险 (ARIC) 研究以及使用基因组学和人口结构的研究流行病学 (PAGE) 联盟。具体来说，它将检查 1987 年至 2004 年间评估的七个不同亚群中的心率变异性、心室复极、心肌缺血和心室异位的测量结果。这七个亚群包括：(1) 5148 名黑人女性，(2) 2002 名西班牙裔女性，以及 ( 3) 在 WHI CT 中，1507 名患有室性异位的白人女性和 1507 名没有心室异位的白人女性；在 ARIC 研究中，(4) 2615 名黑人女性，(5) 5989 名白人女性，(6) 1621 名黑人男性，(7) 5369 名白人男性。亚群 1-7 将用于独立识别 Affymetrix 6.0 阵列上基因分型的约 106 个单核苷酸多态性 (SNP) 与在地理编码参与者地址空间插值的每日平均环境 PM 浓度之间的基因与环境之间的相互作用。 SNP 主要效应也将被研究。校内共同资助的分析将是强有力的，并针对多重比较进行适当调整。预期的结果将为检查跨种族和性别关联的一致性提供基础。总的来说，他们将促进对生活在美国环境保护署 (EPA) 1-10 区的 25,758 名具有种族和地理代表性的参与者的 PM 介导的心律失常的遗传易感性和病理生理机制的理解。这一进展将有助于深入了解PM引起的心电图异常的比例，通过建立和遵守更严格的国家环境空气质量标准可以减少这些异常。 公共健康相关性：拟议的研究将有效促进对 PM 介导的心律失常发生的遗传易感性和病理生理机制的理解，该人群是居住在美国环境保护署 (EPA) 1-1 区的具有种族和地理代表性的 25,758 名具有统一特征的参与者。 10.其基本原理源于环境颗粒物空气污染水平与急性冠心病事件之间已建立的但异质的关联，急性冠心病是对公众健康的一种广泛但鲜为人知的威胁。