Arsenic Methyltransferase and Apolipoprotein E Polymorphism in Pregnant Women Exposed to Inorganic Arsenic in Drinking Water in Western Romania

TL;DR

This study examines how genetic variations in pregnant women affect arsenic metabolism and pregnancy loss in those exposed to low levels of arsenic in drinking water.

Contribution

The study identifies specific AS3MT haplotypes linked to arsenic metabolite levels and potential pregnancy loss in low-level arsenic-exposed populations.

Findings

Haplotype 1 in AS3MT is associated with higher levels of urinary DMA and MMA, indicating greater arsenic exposure.

Haplotype 4 is linked to lower MMA and DMA levels compared to Haplotype 1, suggesting a protective effect.

AS3MT gene variations appear to influence arsenic metabolism in pregnant women with low-level drinking water exposure.

Abstract

Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in AS3MT and APOE genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified AS3MT polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in AS3MT SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the AS3MT gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure.

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