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Polymorphisms in arsenic(+III)methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism
Engström, Karin (Avtor), Vahter, Marie (Avtor), Jurković Mlakar, Simona (Avtor), Concha, Gabriela (Avtor), Barbro, Nermell (Avtor), Ragib, Rubhana (Avtor), Cardozo, Alejandro (Avtor), Broberg, Karin (Avtor)

URLURL - Predstavitvena datoteka, za dostop obiščite http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1289%2Fehp.1002471 Novo okno

Izvleček
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.

Jezik:Angleški jezik
Ključne besede:arzen, polimorfizem, genska ekspresija, AS3MT
Vrsta gradiva:Delo ni kategorizirano (r6)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:FFA - Fakulteta za farmacijo
Leto izida:2011
Št. strani:str. 182-188
Številčenje:Vol. 119, no. 2
UDK:577
ISSN pri članku:0091-6765
DOI:10.1289/ehp.1002471 Povezava se odpre v novem oknu
COBISS.SI-ID:2873457 Povezava se odpre v novem oknu
Število ogledov:555
Število prenosov:86
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
 
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Gradivo je del revije

Naslov:Environmental health perspectives
Skrajšan naslov:Environ. health perspect.
Založnik:U.S. Department of Health and Human Services, Public Health Service
ISSN:0091-6765
COBISS.SI-ID:37553409 Novo okno

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