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Polymorphisms in arsenic(+III)methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolismEngström, Karin ...Background: Arsenic is mono- (MMA) and dimethylated (DMA) in humans and the methylation pattern demonstrates large inter-individual differences. The fraction of urinary MMA is a marker for ... susceptibility to arsenic-related diseases. Objectives: The impact of polymorphisms in five methyltransferase genes on arsenic metabolism was evaluated in two populations, one in South America, one in southeast Asia. The methyltransferase genes were arsenic(+III)methyltransferase (AS3MT), DNAmethyltransferase 1a and 3b (DNMT1a, DNMT3b), phosphatidylethanolamine Nmethyltransferase (PEMT) and betaine-homocysteine methyltransferase (BHMT). AS3MT expression was analyzed in peripheral blood. Methods: Subjects were women, exposed to arsenic in drinking water in the Argentinean Andes (N=172; median urinary arsenic 200 [micro]g/L) and in rural Bangladesh (N=361; 100g/L, all in early pregnancy). Urinary arsenic metabolites were measured by HPLC-ICPMS. Polymorphisms (N=22) were genotyped with SequenomTM. AS3MT expression was measured with qPCR using TaqManr expression assays. Results: Six AS3MT polymorphisms were significantly associated with arsenic metabolite patterns in both populations (p-values ?0.01). The most frequent AS3MT haplotype in Bangladesh was associated with higher %MMA, and the most frequent in Argentina with lower %MMA and higher %DMA. Four polymorphisms in the DNMTs were associated with metabolite patterns in Bangladesh. Non-coding AS3MT polymorphisms affected gene expression of AS3MT in peripheral blood, demonstrating that one functional impact of AS3MT polymorphisms may be altering levels of gene expression. Conclusions: Polymorphisms in AS3MT significantly predicted As metabolism across these two very different populations, suggesting that AS3MT may have an impact on As metabolite patterns in populations worldwide.Source: Environmental health perspectives. - ISSN 0091-6765 (Vol. 119, no. 2, 2011, str. 182-188)Type of material - article, component partPublish date - 2011Language - englishCOBISS.SI-ID - 2873457
Author
Engström, Karin |
Vahter, Marie |
Jurković Mlakar, Simona, 1980- |
Concha, Gabriela |
Barbro, Nermell |
Ragib, Rubhana |
Cardozo, Alejandro |
Broberg, Karin
Topics
arzen |
polimorfizem |
genska ekspresija |
AS3MT
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Engström, Karin | ![]() |
Vahter, Marie | ![]() |
Jurković Mlakar, Simona, 1980- | 27741 |
Concha, Gabriela | ![]() |
Barbro, Nermell | ![]() |
Ragib, Rubhana | ![]() |
Cardozo, Alejandro | ![]() |
Broberg, Karin | ![]() |
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