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Low-Level Environmental Cadmium Exposure is Associated with DNA Hypomethylation in Argentinean Women.

Författare:
Publiceringsår: 2012
Språk: Engelska
Sidor: 879-884
Publikation/Tidskrift/Serie: Environmental health perspectives
Volym: 120
Nummer: 6
Dokumenttyp: Artikel
Förlag: National Institute of Environmental Health Sciences

Sammanfattning

Background: Cadmium, a common food pollutant, alters DNA methylation in vitro. Epigenetic effects might therefore partly explain cadmium's toxicity, including carcinogenicity, but human data on epigenetic effects are lacking. Objectives: To evaluate effects of dietary cadmium exposure on DNA methylation, considering other environmental exposures, genetic predisposition, and gene expression.

Methods: Concentrations of cadmium, arsenic, selenium and zinc in blood and urine of nonsmoking women (N=202) from the Northern Argentinean Andes were measured by ICP-MS. Methylation in CpG islands of LINE1 (proxy for global DNA methylation) and promoter regions of p16 (CDKN2A) and MLH1 in peripheral blood were measured by bisulfite PCR pyrosequencing. Genotyping (N=172) for DNMT1 (rs10854076, rs2228611) and DNMT3B (rs2424913, rs2424932) was performed with SequenomTM; and gene expression (N=90) with DirectHyb HumanHT-12 v3.0.

Results: Cadmium exposure was low: median concentrations in blood and urine were 0.36 and 0.23 µg/L, respectively. Urinary cadmium (ln transformed) was inversely associated with LINE1 methylation (β=-0.50, p=0.0070; β=-0.44, p=0.026 adjusted for age and coca chewing), but not with p16 or MLH1 methylation. Both DNMT1 rs10854076 and DNMT1 rs2228611 polymorphisms modified associations between urinary cadmium and LINE1 (p-values for interaction in adjusted models were 0.045 and 0.064, respectively). The rare genotypes demonstrated stronger hypomethylation with increasing urinary cadmium concentrations. Cadmium was inversely associated with DNMT3B (rs -0.28, p=0.0086), but not with DNMT1 expression (rs -0.075, p=0.48).

Conclusion: Environmental cadmium exposure was associated with DNA hypomethylation in peripheral blood and DNMT1 genotypes modified this association. The role of epigenetic modifications in cadmium-associated diseases needs clarification.

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Nyckelord

  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 1552-9924

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