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）：拟议的研究检查了对颗粒物质（PM）空气污染的心律不齐作用的敏感性，这是由常见遗传变异所促进的。它的理由源于既定的，但异质的关联PM空气污染与急性冠心病（CHD）事件，这是一种广泛但对公共卫生的威胁，这是一个广泛的，但知之甚少。它的重点是静止，标准的十二个铅ECG测量，一方面与环境PM浓度有关，另一方面与急性CHD事件有关。 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基因组学和流行病学（页）财团。具体而言，它将在1987年至2004年之间评估的七个不同的亚种群中检查心率变异性，心室复极化，心肌缺血和心室外观的措施。（1）5148个黑人女性，（2）2002年西班牙裔女性，以及（3）1507白色女性，没有concoppy和1507年的白色女性，无效。在ARIC研究中，（4）2615名黑人妇女，（5）5989名白人妇女，（6）1621个黑人男性和（7）5369名白人男性。亚群1-7将用于独立鉴定在Affymetrix 6.0阵列上的大约106个单核苷酸多态性（SNP）之间的基因 - 环境相互作用与每日平均环境PM浓度在地理编码参与者地址上空间插值。 SNP的主要影响也将被研究。由校内共同资助的分析将得到充分的动力，并适当调整以进行多次比较。预期的发现将为研究整个种族和性别的协会的一致性提供基础。总的来说，他们将提高对PM介导的心律失常基础的遗传易感性以及在美国环境保护署（EPA）区域中占有良好特征良好的参与者（EPA）区域1-10的种族和地理代表性人群中的病理生理机制。进步将提供有关可通过建立和遵守更严格的国家环境空气质量标准来降低的可降低PM侵入性心电图异常比例的洞察力。 公共卫生相关性：拟议的研究将有效地提高对遗传易感性以及PM介导的心律不齐的基础的遗传易感性以及在美国环境保护局（EPA）地区（EPA）1-10的种族和地理位置代表性的人口中的心律失常发生。它的理由源于颗粒物空气污染的环境水平与急性冠心病事件之间的既定但异质关联，这是一种广泛的，但对公共卫生的威胁知之甚少。