title: Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh.
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.
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Fen
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Center, 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; The University of Chicago Comprehensive Cancer Center, Chicago, IL, USA.
authors.forename: Muhammad G
authors.initials: MG
authors.lastname: Kibriya
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Mengling
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY, USA.
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Center, Chicago, IL, USA.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Paul-Brutus
authors.affiliation: U-Chicago Research Bangladesh, Ltd., Dhaka, Bangladesh.
authors.forename: Rina Rani
authors.initials: RR
authors.lastname: Paul
authors.affiliation: U-Chicago Research Bangladesh, Ltd., Dhaka, Bangladesh.
authors.forename: Golam
authors.initials: G
authors.lastname: Sarwar
authors.affiliation: U-Chicago Research Bangladesh, Ltd., Dhaka, Bangladesh.
authors.forename: Alauddin
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Population Health, New York University School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Jieying
authors.initials: J
authors.lastname: Jiang
authors.affiliation: U-Chicago Research Bangladesh, Ltd., Dhaka, Bangladesh.
authors.forename: Tariqul
authors.initials: T
authors.lastname: Islam
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY, USA.
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.affiliation: Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Demmer
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY, USA.
authors.forename: Moise
authors.initials: M
authors.lastname: Desvarieux
authors.affiliation: Department of Health Studies, The University of Chicago, Chicago, IL, USA; The University of Chicago Comprehensive Cancer Center, 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; Department of Environmental Medicine, 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: D000328:Adult; D001151:Arsenic / Q000009:adverse effects*; D001459:Bangladesh; D002318:Cardiovascular Diseases / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014874:Water Pollutants, Chemical / Q000009:adverse effects*; D014881:Water Supply / Q000032:analysis
chemical_list: D014874:Water Pollutants, Chemical; D008780:Methyltransferases; C505756:AS3MT protein, human; D001151:Arsenic
keywords: Arsenic; Bangladesh; Cardiovascular diseases; Carotid artery intima–media thickness; Drinking water; Single nucleotide polymorphism