Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The susceptibility to arsenic-induced diseases differs greatly between individuals, possibly due to interindividual variations in As metabolism that affect retention and distribution of toxic metabolites. To elucidate the role of genetic factors in As metabolism, we studied how polymorphisms in six genes affected the urinary metabolite pattern in a group of indigenous women (n = 147) in northern Argentina who were exposed to approximately 200 mu g/L As in drinking water. These women had low urinary percentages of monomethylated As (MMA) and high percentages of dimethylated As (DMA). MMA has been associated with adverse health effects, and DMA has the lowest body retention of the metabolites. The genes studied were arsenic(+ 111) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferases mu I (GSTM1) and theta I (GSTT1). We found three intronic polymorphisms in AS3MT (G12390C, C14215T, and G35991A) associated with a lower percentage of MMA (%MMA) and a higher percentage of DMA (%DMA) in urine. The variant homozygotes showed approximately half the %MMA compared with wild-type homozygotes. These polymorphisms were in strong linkage, with high allelic frequencies (72-76%) compared with other populations. We also saw minor effects of other polymorphisms in the multivariate regression analysis with effect modification for the deletion genotypes for GSTM1 (affecting %MMA) and GSTT1 (affecting %MMA and %DMA). For pregnant women, effect modification was seen for the folate-metabolizing genes MTR and MTHFA In conclusion, these findings indicate that polymorphisms in AS3MT-and possibly GSTM1, GSTT1, MTR, and MTHFR-are responsible for a large part of the interindividual variation in As metabolism and susceptibility.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Miljömedicin och yrkesmedicin

Nyckelord

Originalspråkengelska
Sidor (från-till)599-605
TidskriftEnvironmental Health Perspectives
Volym115
Utgivningsnummer4
StatusPublished - 2007
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Karin Engström, 2010, Division of Occupational and Environmental Medicine. 138 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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