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  • Engström, KarinLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine (author)

Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina.

  • Article/chapterEnglish2007

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  • Environmental Health Perspectives,2007

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  • LIBRIS-ID:oai:lup.lub.lu.se:2eb4b24f-36a8-4dc7-9523-98cbf743a6f2
  • https://lup.lub.lu.se/record/167428URI
  • https://doi.org/10.1289/ehp.9734DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:14551368URI

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  • Language:English
  • Summary in:English

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  • 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.

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  • Broberg Palmgren, KarinLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-kbr (author)
  • Concha, Gabriela (author)
  • Nermell, BarbroKarolinska Institutet (author)
  • Warholm, MargaretaKarolinska Institutet (author)
  • Vahter, MarieKarolinska Institutet (author)
  • Avdelningen för arbets- och miljömedicinInstitutionen för laboratoriemedicin (creator_code:org_t)

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  • In:Environmental Health Perspectives: Environmental Health Perspectives115:4, s. 599-6051552-99240091-6765

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