Genetic Polymorphisms Influencing Arsenic Metabolism in Human: Evidence from Vietnam

We report the association of levels of urinary arsenic (As) compounds (arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), and arsenobetaine (AB)) with genetic polymorphisms of candidate genes, glutathione S-transferase omega 1 (GSTO1) and 2 (GSTO2), mu 1 (GSTM1), and theta 1 (GSTT1), arsenic (+3 oxidation state) methyltransferase (AS3MT), methylenetetrahydrofolate reductase (MTHFR), and DNA repair gene XPD in 100 subjects from Ha Nam Province in the Red River Delta, Vietnam. No significant relationship between As levels and genetic polymorphisms of GSTT1 and MTHFR was observed. GSTM1 null was found to be associated with increased percentage of urinary DMAV. High concentrations of AsV in urine were observed in individuals with Asn142Asp genotype of GSTO2. Subjects with gene polymorphisms of Glu155del in GSTO1 and Met287Thr in AS3MT had higher ratios of urinary MMAV/(AsIII + AsV) indicating higher capacity for primary As methylation. We found that intronic polymorphisms of G12390C wild-type homozygosity and G35991A variant-type homozygosity in AS3MT were associated with lower DMAV/ MMAV and DMAV percentages in urine, respectively. Percentages of AsIII in the urine of subjects with Lys751Gln genotype in XPD were higher than those with wild type. From our findings, it can be concluded that genetic polymorphisms in GSTM1, GSTO1, GSTO2, AS3MT, and XPD may be responsible for As metabolism and toxicity in Vietnamese.