title: Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.
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 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.
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA; Department of Population Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Shohreh F
authors.initials: SF
authors.lastname: Farzan
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Jieying
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Fen
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA.
authors.forename: Mengling
authors.initials: M
authors.lastname: Liu
authors.affiliation: The Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Newman
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Farzana
authors.initials: F
authors.lastname: Jasmine
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Muhammad G
authors.initials: MG
authors.lastname: Kibriya
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Paul-Brutus
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Argos
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Scannell Bryan
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Mahbub
authors.initials: M
authors.lastname: Eunus
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Alauddin
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rakibuz-Zaman
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Rabiul
authors.initials: R
authors.lastname: Hasan
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Golam
authors.initials: G
authors.lastname: Sarwar
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Graziano
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; Department of Medicine and Human Genetics, The University of Chicago, Chicago, IL, USA; Department of Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA. Electronic address: yu.chen@nyumc.org.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001151:Arsenic / Q000009:adverse effects*; D001459:Bangladesh; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000009:adverse effects*; D060986:Water Wells; D055815:Young Adult
chemical_list: D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: Arsenic; Blood pressure; CYBA; HEALS; Longitudinal; SNPs