Common genetic variation, residential proximity to traffic exposure, and left ventricular mass: the multi-ethnic study of atherosclerosis.
Common genetic variation, residential proximity to traffic exposure, and left ventricular mass: the multi-ethnic study of atherosclerosis.
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DOI：
10.1289/ehp.0901535
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发表时间：
2010-07
影响因子：
10.4
通讯作者：
Kaufman JD
中科院分区：
文献类型：
--
作者：
Van Hee VC;Adar SD;Szpiro AA;Barr RG;Diez Roux A;Bluemke DA;Sheppard L;Gill EA;Bahrami H;Wassel C;Sale MM;Siscovick DS;Rotter JI;Rich SS;Kaufman JD
左心室质量 (LVM) 升高是不良心血管结局的强烈预测因素，包括心力衰竭、中风和心源性猝死。先前已经描述过住宅靠近主要道路（< 50 m 与 > 150 m）与较高 LVM 之间的关系，但这种关系中涉及的机制途径尚不清楚。了解影响这些效应易感性的遗传因素可能有助于深入了解相关的机制途径。我们着手确定影响血管和自主神经功能、血压或炎症的基因的遗传多态性是否会影响交通邻近度和 LVM 之间的关系。这是一项对动脉粥样硬化多种族研究中 1,376 名基因分型参与者进行的横断面研究，在 2000 年至 2002 年间进行了心脏磁共振成像。标记单核苷酸多态性 (tagSNP) 和推断单倍型对 12 个候选基因（ACE、ADRB2、AGT、AGTR1、ALOX15、EDN1、GRK4、使用多元线性回归分析了住宅邻近主要道路与 LVM 之间的关系（PTGS1、PTGS2、TLR4、VEGFA 和 VEGFB），并调整了多个潜在的混杂因素。经过多次测试和比较纯合子后，1 型血管紧张素 II 受体（AGTR1，rs6801836）和花生四烯酸 15-脂氧合酶（ALOX15，rs2664593）基因中的 tagSNP 均与住宅邻近主要道路和 LVM 之间的关联存在 9-10% 的显着相关性（q < 0.2）。血压控制不佳的参与者表现出 AGTR1 与交通邻近度之间更强的相互作用。负责血管功能、炎症和氧化应激的基因中常见的多态性似乎改变了靠近主要道路和 LVM 之间的关联。进一步了解基因如何改变空气污染对心血管疾病的影响可能有助于指导研究工作进入特定的机制途径。
Elevated left ventricular mass (LVM) is a strong predictor of negative cardiovascular outcomes, including heart failure, stroke, and sudden cardiac death. A relationship between close (< 50 m compared with > 150 m) residential proximity to major roadways and higher LVM has previously been described, but the mechanistic pathways that are involved in this relationship are not known. Understanding genetic factors that influence susceptibility to these effects may provide insight into relevant mechanistic pathways. We set out to determine whether genetic polymorphisms in genes affecting vascular and autonomic function, blood pressure, or inflammation influence the relationship between traffic proximity and LVM. This was a cross-sectional study of 1,376 genotyped participants in the Multi-Ethnic Study of Atherosclerosis, with cardiac magnetic resonance imaging performed between 2000 and 2002. The impact of tagged single-nucleotide polymorphisms (tagSNPs) and inferred haplotypes in 12 candidate genes (ACE, ADRB2, AGT, AGTR1, ALOX15, EDN1, GRK4, PTGS1, PTGS2, TLR4, VEGFA, and VEGFB) on the relationship between residential proximity to major roadways and LVM was analyzed using multiple linear regression, adjusting for multiple potential confounders. After accounting for multiple testing and comparing homozygotes, tagSNPs in the type 1 angiotensin II receptor (AGTR1, rs6801836) and arachidonate 15-lipoxygenase (ALOX15, rs2664593) genes were each significantly (q < 0.2) associated with a 9–10% difference in the association between residential proximity to major roadways and LVM. Participants with suboptimal blood pressure control demonstrated stronger interactions between AGTR1 and traffic proximity. Common polymorphisms in genes responsible for vascular function, inflammation, and oxidative stress appear to modify associations between proximity to major roadways and LVM. Further understanding of how genes modify effects of air pollution on CVD may help guide research efforts into specific mechanistic pathways.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
8.3
作者：
Bevan, Steve;Lorenz, Matthias W.;Markus, Hugh S.
通讯作者：
Markus, Hugh S.
影响因子：
5
作者：
Bild, DE;Bluemke, DA;Tracy, RP
通讯作者：
Tracy, RP
影响因子：
4.8
作者：
Gradman, Alan H.
通讯作者：
Gradman, Alan H.
影响因子：
2
作者：
HOCHBERG, Y;BENJAMINI, Y
通讯作者：
BENJAMINI, Y