Ainash Childebayeva1, Jaclyn M Goodrich2, Nathan Chesterman3, Fabiola Leon-Velarde4, Maria Rivera-Ch4, Melisa Kiyamu4, Tom D Brutsaert5, Abigail W Bigham6, Dana C Dolinoy7. 1. Department of Anthropology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena 07745, Germany. Electronic address: childebayeva@shh.mpg.de. 2. Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. 3. School for Environment and Sustainability, University of Michigan, Ann Arbor, MI 48109, USA. 4. Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru. 5. Department of Exercise Science, Syracuse University, Syracuse, NY 13244, USA. 6. Department of Anthropology, University of California, Los Angeles, CA 90095, USA. 7. Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
Abstract
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.
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.
Authors: Jens Bertram; Christian Ramolla; André Esser; Thomas Schettgen; Nina Fohn; Jasmina Steib; Thomas Kraus Journal: Environ Sci Pollut Res Int Date: 2022-10-20 Impact factor: 5.190
Authors: Jens Bertram; Christian Ramolla; André Esser; Thomas Schettgen; Nina Fohn; Thomas Kraus Journal: Int J Environ Res Public Health Date: 2022-05-17 Impact factor: 4.614