title: Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic.
abstract: Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer.
authors: Arsenic Health Effects Research Program, School of Public Health, University of California, Berkeley, California, USA.
authors: Craig
authors: C
authors: Steinmaus
authors: Lee E
authors: LE
authors: Moore
authors: Miriam
authors: M
authors: Shipp
authors: David
authors: D
authors: Kalman
authors: Omar A
authors: OA
authors: Rey
authors: Mary L
authors: ML
authors: Biggs
authors: Claudia
authors: C
authors: Hopenhayn
authors: Michael N
authors: MN
authors: Bates
authors: Shichun
authors: S
authors: Zheng
authors: John K
authors: JK
authors: Wiencke
authors: Allan H
authors: AH
authors: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001118:Argentina / Q000453:epidemiology; D001151:Arsenic / Q000652:urine*; D001152:Arsenicals / Q000652:urine*; D016022:Case-Control Studies; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000652:urine*; D062665:Epidemiological Monitoring; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008745:Methylation; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000652:urine
chemical_list: D001151:Arsenic; D001152:Arsenicals; D004785:Environmental Pollutants; D005982:Glutathione Transferase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C413545:glutathione S-transferase T1