TY - JOUR
T1 - Interaction between arsenic exposure from drinking water and genetic polymorphisms on cardiovascular disease in Bangladesh
T2 - A prospective case-cohort study
AU - Wu, Fen
AU - Jasmine, Farzana
AU - Kibriya, Muhammad G.
AU - Liu, Mengling
AU - Cheng, Xin
AU - Parvez, Faruque
AU - Islam, Tariqul
AU - Ahmed, Alauddin
AU - Rakibuz-Zaman, Muhammad
AU - Jiang, Jieying
AU - Roy, Shantanu
AU - Paul ‑ Brutus, Rachelle
AU - Slavkovich, Vesna
AU - Islam, Tariqul
AU - Levy, Diane
AU - Vanderweele, Tyler J.
AU - Pierce, Brandon L.
AU - Graziano, Joseph H.
AU - Ahsan, Habibul
AU - Chen, Yu
N1 - Publisher Copyright:
© 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved.
PY - 2015
Y1 - 2015
N2 - Background: Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited. Objective: 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. Method: 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. Results: 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. Conclusions: Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction.
AB - Background: Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited. Objective: 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. Method: 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. Results: 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. Conclusions: Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction.
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U2 - 10.1289/ehp.1307883
DO - 10.1289/ehp.1307883
M3 - Article
C2 - 25575156
AN - SCOPUS:84938373299
SN - 0091-6765
VL - 123
SP - 451
EP - 457
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 5
ER -