Wu Fen, Jasmine Farzana, Kibriya Muhammad G, Liu Mengling, Cheng Xin, Parvez Faruque, Islam Tariqul, Ahmed Alauddin, Rakibuz-Zaman Muhammad, Jiang Jieying, Roy Shantanu, Paul-Brutus Rachelle, Slavkovich Vesna, Islam Tariqul, Levy Diane, VanderWeele Tyler J, Pierce Brandon L, Graziano Joseph H, Ahsan Habibul, Chen Yu
Department of Population Health, New York University School of Medicine, New York, New York, USA.
Environ Health Perspect. 2015 May;123(5):451-7. doi: 10.1289/ehp.1307883. Epub 2015 Jan 9.
Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited.
We investigated whether the association between well-water arsenic and cardiovascular disease (CVD) differed by 170 single nucleotide polymorphisms (SNPs) in 17 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction.
We conducted a prospective case-cohort study nested in the Health Effects of Arsenic Longitudinal Study, with a random subcohort of 1,375 subjects and 447 incident fatal and nonfatal cases of CVD. Well-water arsenic was measured in 2000 at baseline. The CVD cases, 56 of which occurred in the subcohort, included 238 coronary heart disease cases, 165 stroke cases, and 44 deaths due to other CVD identified during follow-up from 2000 to 2012.
Of the 170 SNPs tested, multiplicative interactions between well-water arsenic and two SNPs, rs281432 in ICAM1 (padj = 0.0002) and rs3176867 in VCAM1 (padj = 0.035), were significant for CVD after adjustment for multiple testing. Compared with those with GC or CC genotype in rs281432 and lower well-water arsenic, the adjusted hazard ratio (aHR) for CVD was 1.82 (95% CI: 1.31, 2.54) for a 1-SD increase in well-water arsenic combined with the GG genotype, which was greater than expected given aHRs of 1.08 and 0.96 for separate effects of arsenic and the genotype alone, respectively. Similarly, the joint aHR for arsenic and the rs3176867 CC genotype was 1.34 (95% CI: 0.95, 1.87), greater than expected given aHRs for their separate effects of 1.02 and 0.84, respectively.
Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction.
关于饮用水中砷暴露对心血管影响的遗传易感性的流行病学数据有限。
我们调查了与砷代谢、氧化应激、炎症和内皮功能障碍相关的17个基因中的170个单核苷酸多态性（SNP）是否会使井水砷与心血管疾病（CVD）之间的关联有所不同。
我们在砷的健康影响纵向研究中进行了一项前瞻性病例队列研究，随机抽取了1375名受试者作为子队列，以及447例CVD的致命和非致命发病病例。2000年在基线时测量了井水砷含量。CVD病例（其中56例发生在子队列中）包括238例冠心病病例、165例中风病例以及在2000年至2012年随访期间确定的44例其他CVD死亡病例。
在测试的170个SNP中，经过多重检验校正后，井水砷与ICAM1基因中的两个SNP（rs281432，padj = 0.0002）以及VCAM1基因中的rs3176867（padj = 0.035）之间的相乘交互作用对CVD具有显著意义。与rs281432中具有GC或CC基因型且井水砷含量较低的人群相比，井水砷含量每增加1个标准差且伴有GG基因型时，CVD的校正风险比（aHR）为1.82（95%CI：1.31，2.54），高于单独砷暴露和单独基因型的aHR分别为1.08和0.96时的预期值。同样，砷与rs3176867 CC基因型的联合aHR为1.34（95%CI：0.95，1.87），高于单独砷暴露和单独基因型的aHR分别为1.02和0.84时的预期值。
CVD与砷暴露之间的关联可能会被与内皮功能障碍相关的基因变异所改变。
