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Title: Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

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 themore » 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. - Highlights: • Nine SNPs had a nominally significant interaction with well-water arsenic in cIMT. • Three SNPs in AS3MT showed nominally significant interactions with urinary arsenic. • cIMT was much higher among subjects with higher arsenic exposure and AS3MT SNPs. • The at-risk genotypes of AS3MT SNPs were positively related to urinary MMA%.« less
Authors:
 [1] ;  [2] ; ;  [3] ;  [2] ; ;  [1] ;  [2] ;  [4] ;  [3] ;  [2] ; ; ; ;  [5] ;  [1] ;  [2] ;  [5] ;  [4] ;  [6] more »;  [2] ; ;  [7] ; « less
  1. Department of Population Health, New York University School of Medicine, New York, NY (United States)
  2. (United States)
  3. Department of Health Studies, The University of Chicago, Chicago, IL (United States)
  4. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY (United States)
  5. U-Chicago Research Bangladesh, Ltd., Dhaka (Bangladesh)
  6. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL (United States)
  7. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY (United States)
Publication Date:
OSTI Identifier:
22439705
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 276; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARSENIC; ARTERIOSCLEROSIS; BANGLADESH; CAROTID ARTERIES; DRINKING WATER; GENES; GENOTYPE; HAZARDS; INDIUM ARSENIDES; INFLAMMATION; METABOLISM; METHYLATION; NUCLEOTIDES; OXIDATION; STRESSES; THICKNESS; URINE