Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic.
Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT-Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT-Met287Thr polymorphism with %MMA and between the GSTO1-Glu155del and As(v) was found; whereas, a negative relationship was identified between AS3MT-Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1-Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516-525, 2016. © 2016 Wiley Periodicals, Inc.
Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico.
Rogelio
R
Recio-Vega
Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico.
Tania
T
González-Cortes
Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico.|Department of Environmental Toxicology, School of Chemical Sciences, University Juarez of Durango, Gomez Palacio, Durango, Mexico.
Edgar
E
Olivas-Calderón
Department of Cellular and Molecular Medicine, Southwest Environmental Health Science Center, University of Arizona, Tucson, Arizona, USA.|Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona, USA.
R
R
Clark Lantz
Department of Cellular and Molecular Medicine, Southwest Environmental Health Science Center, University of Arizona, Tucson, Arizona, USA.|Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA.
A
A
Jay Gandolfi
Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila, Mexico.
Gladis
G
Michel-Ramirez
D001151:Arsenic / Q000378:metabolism / Q000652:urine*; D002648:Child; D004781:Environmental Exposure / Q000032:analysis; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics*; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012737:Sex Factors; D013997:Time Factors; D014505:Urban Population; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000652:urine*
D001151:Arsenic; D005982:Glutathione Transferase; D008780:Methyltransferases; D014874:Water Pollutants, Chemical; C505756:AS3MT protein, human; C413545:glutathione S-transferase T1; C490476:GSTO1 protein, human
AS3MT; GSTM1; GSTO1; GSTT1; arsenic; children