Interaction between arsenic exposure from drinking water and genetic polymorphisms on cardiovascular disease in Bangladesh: a prospective case-cohort study.

Abstract

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.

• Authors: Fen Wu, Farzana Jasmine, Muhammad G Kibriya, Mengling Liu, Xin Cheng, Faruque Parvez, Tariqul Islam, Alauddin Ahmed, Muhammad Rakibuz-Zaman, Jieying Jiang, Shantanu Roy, Rachelle Paul-Brutus, Vesna Slavkovich, Tariqul Islam, Diane Levy, Tyler J VanderWeele, Brandon L Pierce, Joseph H Graziano, Habibul Ahsan, Yu Chen
• Journal: Environmental health perspectives (Environ Health Perspect) Vol. 123 Issue 5 Pg. 451-7 (May 2015) ISSN: 1552-9924 [Electronic] United States
• PMID: 25575156 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Drinking Water
• ICAM1 protein, human
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Arsenic

Topics

• Adult
• Arsenic (toxicity)
• Bangladesh (epidemiology)
• Cardiovascular Diseases (epidemiology, genetics)
• Drinking Water (adverse effects)
• Environmental Exposure
• Female
• Genotype
• Humans
• Intercellular Adhesion Molecule-1 (genetics)
• Male
• Middle Aged
• Polymorphism, Genetic (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Prospective Studies
• Stroke (genetics)
• Vascular Cell Adhesion Molecule-1 (genetics)