Nutrient-Gene Interaction in Arsenic Metabolism

Abstract

Arsenic (As) naturally occurs in water and its long-term exposure is linked with many health problems, including skin lesions and cancer. Nutrient intake and genetic polymorphisms involved in one-carbon metabolism, including the choline pathway, may explain inter-individual variation in As metabolism and elimination, possibly influencing susceptibility to As-related disease. To examine As metabolism and elimination efficiency in relation to intake of choline, betaine, and methionine, and choline dehydrogenase (CHDH) rs7626693 and betaine homocysteine methyltransferase (BHMT) rs3733890 genetic variants. Women (n=415) from As-exposed regions of Northern Mexico, were interviewed and provided biological samples. Nutrient intake was estimated using a validated semi-quantitative food frequency questionnaire. Urinary As species were determined with HPLC-ICP-MS and the relative proportions and ratios of As metabolism were calculated. Genetic polymorphisms were genotyped via allelic discrimination. Multivariate linear regression models were developed to evaluate the associations between nutrients, polymorphisms and urinary As parameters In gene-nutrient adjusted models, methionine was the only nutrient significantly associated with As metabolism. After adjusting for BHMT, methionine was associated with lower percentage of inorganic As (%iAs) and higher percentage of dimethylarsinic acid (%DMA) and total methylation index (DMA/iAs). Among women with the GG+AG genotypes of BHMT, methionine was additionally associated with lower percentage of monomethylarsonic acid (%MMA) and higher secondary methylation index (DMA/MMA). A statistically significant interaction between methionine and BHMT was detected. Conclusion. Nutrients may play a role in As metabolism, particularly within certain genetic variant subgroups, via one-carbon and choline pathways. Differences in nutrient intake and genetic polymorphisms may jointly influence As metabolism and elimination efficiency.