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

Fen Wu, Farzana Jasmine, Muhammad G. Kibriya, Mengling Liu, Xin Cheng, Faruque Parvez, Rachelle Paul-Brutus, Tariqul Islam, Rina Rani Paul, Golam Sarwar, Alauddin Ahmed, Jieying Jiang, Tariqul Islam, Vesna Slavkovich, Tatjana Rundek, Ryan T. Demmer, Moise Desvarieux, Habibul Ahsan, Yu Chen

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)195-203
Number of pages9
JournalToxicology and Applied Pharmacology
Volume276
Issue number3
DOIs
StatePublished - May 1 2014

Keywords

  • Arsenic
  • Bangladesh
  • Cardiovascular diseases
  • Carotid artery intima-media thickness
  • Drinking water
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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