title: Interaction between arsenic exposure from drinking water and genetic polymorphisms on cardiovascular disease in Bangladesh: a prospective case-cohort study.
abstract: BACKGROUND
  Epidemiologic data on genetic susceptibility to cardiovascular effects of arsenic exposure from drinking water are limited.
  
  
  OBJECTIVE
  We investigated whether the association between well-water arsenic and cardiovascular disease (CVD) differed by 170 single nucleotide polymorphisms (SNPs) in 17 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction.
  
  
  METHODS
  We conducted a prospective case-cohort study nested in the Health Effects of Arsenic Longitudinal Study, with a random subcohort of 1,375 subjects and 447 incident fatal and nonfatal cases of CVD. Well-water arsenic was measured in 2000 at baseline. The CVD cases, 56 of which occurred in the subcohort, included 238 coronary heart disease cases, 165 stroke cases, and 44 deaths due to other CVD identified during follow-up from 2000 to 2012.
  
  
  RESULTS
  Of the 170 SNPs tested, multiplicative interactions between well-water arsenic and two SNPs, rs281432 in ICAM1 (padj = 0.0002) and rs3176867 in VCAM1 (padj = 0.035), were significant for CVD after adjustment for multiple testing. Compared with those with GC or CC genotype in rs281432 and lower well-water arsenic, the adjusted hazard ratio (aHR) for CVD was 1.82 (95% CI: 1.31, 2.54) for a 1-SD increase in well-water arsenic combined with the GG genotype, which was greater than expected given aHRs of 1.08 and 0.96 for separate effects of arsenic and the genotype alone, respectively. Similarly, the joint aHR for arsenic and the rs3176867 CC genotype was 1.34 (95% CI: 0.95, 1.87), greater than expected given aHRs for their separate effects of 1.02 and 0.84, respectively.
  
  
  CONCLUSIONS
  Associations between CVD and arsenic exposure may be modified by genetic variants related to endothelial dysfunction.
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, New York, USA.
authors.forename: Fen
authors.initials: F
authors.lastname: Wu
authors.forename: Farzana
authors.initials: F
authors.lastname: Jasmine
authors.forename: Muhammad G
authors.initials: MG
authors.lastname: Kibriya
authors.forename: Mengling
authors.initials: M
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.forename: Alauddin
authors.initials: A
authors.lastname: Ahmed
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rakibuz-Zaman
authors.forename: Jieying
authors.initials: J
authors.lastname: Jiang
authors.forename: Shantanu
authors.initials: S
authors.lastname: Roy
authors.forename: Rachelle
authors.initials: R
authors.lastname: Paul-Brutus
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: VanderWeele
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Pierce
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000328:Adult; D001151:Arsenic / Q000633:toxicity*; D001459:Bangladesh / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D060766:Drinking Water / Q000009:adverse effects*; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D020521:Stroke / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D060766:Drinking Water; C573420:ICAM1 protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D001151:Arsenic