Association of methionine synthase rs1805087 polymorphism with arsenic-related skin pigmentary changes: a population-based case–control study

Abstract

Objective: Chronic arsenic exposure causes skin lesions including skin cancers, pigmentary changes, and keratosis. Genetic polymorphism in arsenic metabolism may increase susceptibility to the development of arsenic-related skin lesions. This study was performed to determine whether arsenic metabolism-related gene variants are associated with arsenic-related pigmentary changes. Methods: This case–control study involved 189 patients with arsenic-related pigmentary changes and 103 controls. Thirty-eight polymorphisms in 10 genes determined by mass spectrometry assay served as candidate drivers of arsenic-induced pigmentary changes. Urine and plasma arsenic levels were determined by inductively coupled plasma mass spectrometry. Hair arsenic concentrations were measured by nondispersive atomic fluorescence spectrometry. Arsenic metabolites in urine were determined using high-pressure liquid chromatography hyphenated with hydride generation and inductively coupled plasma mass spectrometry. Serum folate was measured using a folate radioassay kit. Analysis of variance, nonparametric test, or the chi-square test was selected according to the data distribution. Spearman correlation analysis was used to determine the correlation between two parameters. Logistic regression was used to estimate the effect size of SNPs. Results: The arsenic concentrations in urine, plasma, and hair and the urine arsenic species were not significantly different between cases and controls. Logistic regression revealed that among the polymorphisms, the methionine synthase (MTR) rs1805087 polymorphism showed a protective effect against arsenic-related pigmentary changes. In the codominant model, the adjusted odds ratio for age, sex, and ethnicity was 0.41 (95% CI, 0.21–0.80; P = 0.008) for the AG genotype and 0.11 (95%CI, 0.02–0.60; P = 0.012) for the GG genotype. Conclusion: MTR polymorphism showed a protective effect against arsenic-related pigmentary changes in the logistic regression model. The effect of MTR rs1805087 might be independent of arsenic metabolism and one-carbon metabolism. More studies are needed to clarify the biological function of MTR rs1805087 and its relationship with the etiology of arsenic-related pigmentary changes.