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Toxicol Appl Pharmacol. 2014 May 1;276(3):195-203. doi: 10.1016/j.taap.2014.02.014. Epub 2014 Mar 2.

Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh.

Author information

1
Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
2
Department of Health Studies, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Center, Chicago, IL, USA.
3
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY, USA.
4
U-Chicago Research Bangladesh, Ltd., Dhaka, Bangladesh.
5
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
6
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY, USA.
7
Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA. Electronic address: yu.chen@nyumc.org.

Abstract

Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = -5.1 μm, 95% CI = -31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = -3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.

KEYWORDS:

Arsenic; Bangladesh; Cardiovascular diseases; Carotid artery intima–media thickness; Drinking water; Single nucleotide polymorphism

PMID:
24593923
PMCID:
PMC4080412
DOI:
10.1016/j.taap.2014.02.014
[Indexed for MEDLINE]
Free PMC Article
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