title: Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh.
abstract: Chronic exposure to arsenic is occurring throughout South and East Asia due to groundwater contamination of well water. Variability in susceptibility to arsenic toxicity may be related to nutritional status. Arsenic is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via one-carbon metabolism, a biochemical pathway that is dependent on folate. The majority of one-carbon metabolism methylation reactions are devoted to biosynthesis of creatine, the precursor of creatinine. Our objectives of this cross-sectional study were to characterize the relationships among folate, cobalamin, homocysteine, and arsenic metabolism in Bangladeshi adults. Water arsenic, urinary arsenic, urinary creatinine, plasma folate, cobalamin, and homocysteine were assessed in 1,650 adults; urinary arsenic metabolites were analyzed for a subset of 300 individuals. The percentage of DMA in urine was positively associated with plasma folate (r = 0.14, p = 0.02) and negatively associated with total homocysteine (tHcys; r = -0.14, p = 0.01). Conversely, percent MMA was negatively associated with folate (r = -0.12, p = 0.04) and positively associated with tHcys (r = 0.21, p = 0.0002); percent inorganic arsenic (InAs) was negatively associated with folate (r = -0.12, p = 0.03). Urinary creatinine was positively correlated with percent DMA (r = 0.40 for males, p < 0.0001; 0.25 for females, p = 0.001), and with percent InAs (r = -0.45 for males, p < 0.0001; -0.20 for females, p = 0.01). Collectively, these data suggest that folate, tHcys, and other factors involved in one-carbon metabolism influence arsenic methylation. This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. mvg7@columbia.edu
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.forename: Richard
authors.initials: R
authors.lastname: Pilsner
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.forename: Pam
authors.initials: P
authors.lastname: Factor-Litvak
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
mesh_terms: D000328:Adult; D001151:Arsenic / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D001152:Arsenicals / Q000652:urine; D001459:Bangladesh; D002101:Cacodylic Acid / Q000652:urine; D003401:Creatine / Q000096:biosynthesis; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000706:statistics & numerical data*; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D005618:Fresh Water; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014805:Vitamin B 12 / Q000097:blood / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000032:analysis*
chemical_list: D001152:Arsenicals; D014874:Water Pollutants, Chemical; D006710:Homocysteine; D005492:Folic Acid; D002101:Cacodylic Acid; D003404:Creatinine; C020300:monomethylarsonic acid; D003401:Creatine; D001151:Arsenic; D014805:Vitamin B 12