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

Abstract

BackgroundGlobal 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.ObjectivesThis study was performed to examine whether low-dose exposure to POPs was associated with global DNA hypomethylation in Koreans.MethodsThe 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.ResultsMost 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.ConclusionsWe found that low-dose exposure to POPs, in particular OC pesticides, was associated with global DNA hypomethylation in apparently healthy Koreans.

DNA methylation in white blood cells

“…Although one study correlated lower levels of LINE-1 with increasing age, 36 most of the studies did not find an agedependent effect on blood LINE-1 methylation. 17,21,[37][38][39][40][41] In contrast, all of the studies investigating age and Alu methylation supported a lower level of DNA methylation of this repetitive element with increasing age. 34,36,37,41 Gene-specific methylation has been correlated with age in some studies ( Table 2).…”

“…17,21,[37][38][39][40][41] In contrast, all of the studies investigating age and Alu methylation supported a lower level of DNA methylation of this repetitive element with increasing age. 34,36,37,41 Gene-specific methylation has been correlated with age in some studies ( Table 2). 34,42 However, studies looking across the genome have found infrequent age-dependent changes in CpG island methylation.…”

“…18 Of the repetitive elements, LINE-1 has been investigated more frequently and was associated with lower levels in females compared to males in most 17,21,[37][38][39]46 but not all studies. 41 In contrast, there has been no consistent pattern associated with Alu methylation. 37,41,46 A genome-wide study of DNA methylation profile among twins and healthy singletons independently found that all CpG sites on the X chromosome were highly methylated in blood DNA from females, consistent with X-inactivation.…”

“…41 In contrast, there has been no consistent pattern associated with Alu methylation. 37,41,46 A genome-wide study of DNA methylation profile among twins and healthy singletons independently found that all CpG sites on the X chromosome were highly methylated in blood DNA from females, consistent with X-inactivation. 44,51 A gender-dependent…”

“…Two studies evaluated the relation between plasma persistent organic pollutant (POP) concentrations and WBC global DNA methylation. 41,57 In 70 Greenlandic Inuit, a population presenting some of the highest reported levels of POP worldwide, a significant inverse linear relationship was found for DDT, DDE, β-hexachlorocyclohexane, oxychlordane, α-chlordane, mirex, several PCBs and the sum of all persistent organic pollutants with Alu methylation. 57 However, as the exposure levels in Greenlandic Inuit are much higher than those in the US general population, it is unclear whether the findings apply to other populations with lower exposures.…”