Academic journal article Environmental Health Perspectives

Association of Low-Dose Exposure to Persistent Organic Pollutants with Global DNA Hypomethylation in Healthy Koreans

Academic journal article Environmental Health Perspectives

Association of Low-Dose Exposure to Persistent Organic Pollutants with Global DNA Hypomethylation in Healthy Koreans

Article excerpt

BACKGROUND: Global DNA methylation levels have been reported to be inversely associated with blood levels of persistent organic pollutants (POPs), xenobiotics that accumulate in adipose tissue. Whether these associations extend to a population with much lower concentrations of POPs is not known.

OBJECTIVES: This study was performed to examine whether low-dose exposure to POPs was associated with global DNA hypomethylation in Koreans.

METHODS: The amount of global DNA hypomethylation was estimated by the percent 5-methyl-cytosine (%5-mC) in Alu and LINE-1 assays in 86 apparently healthy Koreans. Among various POPs, organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenylethers (PBDEs) were measured.

RESULTS: Most OC pesticides were inversely and significantly associated with %5-mC in the Alu assay, with correlation coefficients in the range -0.2 to -0.3 after adjusting for age, sex, body mass index, smoking, and alcohol. The strongest OC pesticide associations with %5-mC in the Alu assay were observed with oxychlordane, trans-nonachlor, and p, p'-dichlorodiphenyldichloroethylene. The correlation coefficient of age with %5-mC in the Alu assay was -0.24, similar to correlations of OC pesticides with %5-mC in the Alu assay. Most PCBs and PBDEs showed nonsignificant inverse trends with %5-mC in the Alu assay, but for some PCBs the U-shaped association was significant. On the other hand, POPs were not associated with %5-mC in the LINE-1 assay.

CONCLUSIONS: We found that low-dose exposure to POPs, in particular OC pesticides, was associated with global DNA hypomethylation in apparently healthy Koreans.

KEY WORDS: epigenetics, hypomethylation, organochlorine pesticides, persistent organic pollutants. Environ Health Perspect 118:370-374 (2010). doi:10.1289/ehp.0901131 available via http://dx.doi. org/ [Online 6 November 2009]

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Recent cross-sectional studies have reported that serum concentrations of persistent organic pollutants (POPs) are associated with a variety of obesity-related diseases including type 2 diabetes and metabolic syndrome in the U.S. general population with only low-dose exposure to POPs (Lee et al. 2006a, 2006b, 2007). In particular, a well-established association between obesity and type 2 diabetes became stronger as serum concentrations of POPs increased, but obesity was not associated with type 2 diabetes among subjects with very low levels of POPs (Lee et al. 2006b).

Even though underlying mechanisms are largely unknown, epigenetic mechanisms have been suggested as a possible explanation for the associations between POPs and various diseases (Porta 2006). DNA methylation constitutes an essential epigenetic characteristic that influences a wide variety of biological processes including gene expression, chromosomal stability, imprinting, and cellular differentiation (Bernstein et al. 2007). Disturbance of epigenetic modulations is considered to be a key mechanism in many diseases (Ozanne and Constancia 2007). In addition, global DNA hypomethylation is thought to constitute an early event in some cancers and can progressively occur and accumulate during aging (Wilson et al. 2007).

Supporting this idea, a recent study among Greenland Inuit has reported that global DNA methylation levels are inversely associated with blood levels of several POPs (Rusiecki et al. 2008). However, as the exposure levels in Greenland Inuit are much higher than those in the U.S. general population, it is unclear whether the findings observed in Greenland Inuit apply to other populations with very low levels of POPs.

This study was performed to examine whether the exposure to low-dose POPs is associated with global DNA hypomethylation of peripheral blood leukocytes in the apparently healthy Korean population. Global DNA hypomethylation was measured by percentage of global genomic DNA methylation, percent 5-methyl-cytosine (%5-mC) in Alu and long interspersed nucleotide element (LINE-1) assays. …

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