4.8 Article

Blood lead levels in Peruvian adults are associated with proximity to mining and DNA methylation

Journal

ENVIRONMENT INTERNATIONAL
Volume 155, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.envint.2021.106587

Keywords

Lead (Pb); Hemoglobin; EWAS; Andes; Mining; DNA methylation

Funding

  1. National Science Foundation [BCS-1132310, BCS-1613415]
  2. Wenner-Gren Foundation Grant
  3. University of Michigan
  4. Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center [P30 ES017885]
  5. Baldwin Fellowship from the L.S.B. Leakey Foundation

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The study found that individuals in Cerro de Pasco had higher levels of Pb compared to those in Lima, with males having higher levels than females. Pb was positively associated with hemoglobin, and in Cerro de Pasco, blood Pb decreased with distance from the mine. Associations were identified between Pb and specific genes related to neurological function through differential methylation analysis.
Background: Inorganic lead (Pb) is common in the environment, and is toxic to neurological, renal, and cardiovascular systems. Pb exposure influences the epigenome with documented effects on DNA methylation (DNAm). We assessed the impact of low levels of Pb exposure on DNAm among non-miner individuals from two locations in Peru: Lima, the capital, and Cerro de Pasco, a highland mining town, to study the effects of Pb exposure on physiological outcomes and DNAm. Methods: Pb levels were measured in whole blood (n = 305). Blood leukocyte DNAm was determined for 90 DNA samples using the Illumina MethylationEPIC chip. An epigenome-wide association study was performed to assess the relationship between Pb and DNAm. Results: Individuals from Cerro de Pasco had higher Pb than individuals from Lima (p-value = 2.00E-16). Males had higher Pb than females (p-value = 2.36E-04). Pb was positively associated with hemoglobin (p-value = 8.60E-04). In Cerro de Pasco, blood Pb decreased with the distance from the mine (p-value = 0.04), and association with soil Pb was approaching significance (p-value = 0.08). We identified differentially methylated positions (DMPs) associated with genes SOX18, ZMIZ1, and KDM1A linked to neurological function. We also found 45 differentially methylated regions (DMRs), seven of which were associated with genes involved in metal ion binding and nine to neurological function and development. Conclusions: Our results demonstrate that even low levels of Pb can have a significant impact on the body including changes to DNAm. We report associations between Pb and hemoglobin, Pb and distance from mining, and between blood and soil Pb. We also report associations between loci- and region-specific DNAm and Pb.

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