Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

Toxicol Appl Pharmacol. 2015 Oct 1;288(1):95-105. doi: 10.1016/j.taap.2015.07.017. Epub 2015 Jul 26.


Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking. In this study, we used mixed effect models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7years of follow-up in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction=0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time.

Keywords: Arsenic; Blood pressure; CYBA; HEALS; Longitudinal; SNPs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arsenic / adverse effects*
  • Bangladesh
  • Blood Pressure / drug effects*
  • Blood Pressure / genetics*
  • Environmental Exposure / adverse effects
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / diagnosis
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Water Pollutants, Chemical / adverse effects*
  • Water Wells
  • Young Adult


  • Water Pollutants, Chemical
  • Arsenic