Blood lead levels and aberrant DNA methylation of the ALAD and p16 gene promoters in children exposed to environmental-lead.

ABSTRACT

BACKGROUND: Lead (Pb) is a well-known toxic heavy metal which can have serious public health hazards. As of today, there is no safe threshold for Pb exposure, especially for children. Lead exposure has been associated with adverse health outcomes involving epigenetic mechanisms, such as aberrant DNA methylation. The objective of the present study was to elucidate the associations between blood lead levels (BLLs) and gene-specific promoter DNA methylation status in environmental Pb-exposed children from Kabwe, Zambia. METHODS: A cross-sectional study was conducted using 2 to 10-year-old children from high Pb exposed area (N = 102) and low Pb exposed area (N = 38). We measured BLLs using a LeadCare II analyzer and investigated the methylation status of the ALAD and p16 gene promoters by methylation-specific PCR. RESULTS: The mean BLLs were 23.7 µg/dL and 7.9 µg/dL in high Pb exposed and low Pb exposed children, respectively. Pb exposure was correlated with increased methylation of the ALAD and p16 genes. The promoter methylation rates of ALAD and p16 in high Pb exposed children were 84.3% and 67.7%, and 42.1% and 44.7% in low Pb exposed children, respectively. Significantly increased methylation was found in both genes in high Pb exposed children compared with low Pb exposed children (p < 0.05). Children with methylated ALAD and p16 genes showed an increased risk of Pb poisoning (odd ratio >1) compared to the unmethylated status. CONCLUSIONS: This study for the first time tries to correlate promoter methylation status of the ALAD and p16 genes in environmental Pb-exposed children from Kabwe, Zambia as a representative. The result suggests that Pb exposure increases aberrations in ALAD and p16 gene methylation, which may be involved in the mechanism of Pb toxicity.