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

Shohreh F. Farzan, Margaret R. Karagas, Jieying Jiang, Fen Wu, Mengling Liu, Jonathan D. Newman, Farzana Jasmine, Muhammad G. Kibriya, Rachelle Paul-Brutus, Faruque Parvez, Maria Argos, Molly Scannell Bryan, Mahbub Eunus, Alauddin Ahmed, Tariqul Islam, Muhammad Rakibuz-Zaman, Rabiul Hasan, Golam Sarwar, Vesna Slavkovich, Joseph GrazianoHabibul Ahsan, Yu Chen

Research output: Contribution to journalArticle

Abstract

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 7. years 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 2.23. mm. Hg (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 0.13. mm. Hg (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.

Original languageEnglish (US)
Pages (from-to)95-105
Number of pages11
JournalToxicology and Applied Pharmacology
Volume288
Issue number1
DOIs
StatePublished - 2015

Keywords

  • Arsenic
  • Blood pressure
  • CYBA
  • HEALS
  • Longitudinal
  • SNPs

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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    Farzan, S. F., Karagas, M. R., Jiang, J., Wu, F., Liu, M., Newman, J. D., Jasmine, F., Kibriya, M. G., Paul-Brutus, R., Parvez, F., Argos, M., Bryan, M. S., Eunus, M., Ahmed, A., Islam, T., Rakibuz-Zaman, M., Hasan, R., Sarwar, G., Slavkovich, V., ... Chen, Y. (2015). Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Toxicology and Applied Pharmacology, 288(1), 95-105. https://doi.org/10.1016/j.taap.2015.07.017