Unlike IGF2/H19 and PEG3, which showed no evidence for association between neonatal lead exposure and DMR methylation, PLAGL1/HYMAI DMR methylation was positively associated with lead levels during this period ([beta] = 0.
These data further indicated that although childhood lead exposure was associated with differences in PEG3 DMR methylation in males and the IGF2/H19 DMR methylation in females, the association between neonatal lead concentrations and PLAGL1/HYMAI DMR methylation may not be sex-specific.
Interestingly, early-childhood but not prenatal or neonatal lead levels were associated with adulthood PEG3 DMR hypomethylation, an association that may be specific to males.
histone modifications and chromatin structure changes); however, similar methylation changes at both the IGF2/H19 and PEG3 DMRs have been associated previously with altered gene expression in human cancers (Cui et al.
Although the small sample size limits inference, this study provides preliminary evidence for significant associations between early lead exposure and DNA methylation at the regulatory regions of PEG3, H19/IGF2, and PLAGL1/HYMAI.
Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation.