Early Life Lead Exposure Causes Gender-Specific Changes in the DNA Methylation Profile of DNA Extracted from Dried Blood Spots

Abstract

Aims: In this paper, we tested the hypothesis that early life lead (Pb) exposure associated DNA methylation (5 mC) changes are dependent on the sex of the child and can serve as biomarkers for Pb exposure. Methods: In this pilot study, we measured the 5mC profiles of DNA extracted from dried blood spots (DBS) in a cohort of 43 children (25 males and 18 females; ages from 3 months to 5 years) from Detroit. Result & Discussion: We found that the effect of Pb-exposure on the 5-mC profiles can be separated into three subtypes: affected methylation loci which are conserved irrespective of the sex of the child (conserved); affected methylation loci unique to males (male-specific); and affected methylation loci unique to females (female-specific).

Keywords::

• blood lead levels
• differential methylation
• DNA methylation
• dried blood spots
• epigenetics
• gene specific
• lead
• whole blood

Supplementary data

Acknowledgements

All of the Infinium data are available upon request to DMR and is available in the GEO database (accession number GSE60598). We thank the Applied Genomics Facility Core at Wayne State University for conducting the HM450K assays.

Financial & competing interests disclosure

This research was supported by R01 ES012933 and R21 ES021893 to DMR, the WSU-NIEHS Center (P30 ES020957), a pilot grant from the Institute for Population Sciences, Health Assessment, Administration, Services and Economics (INPHAASE) from Wayne State University and Henry Ford Medical Center to DM Ruden and MO Dereski, and a National Health and Nutrition Examination Survey), BLEEP (The Michigan Bloodspot Environmental Epidemiology Project) pilot grant from the University Research Corridor (URC) to DM Ruden. ICP-MS analyses were supported by NSF grant DUE-9952410 to K Hollacher. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Internal Review Board (IRB) approval for this study was granted by Wayne State University, the Michigan Department of Community Health and the Michigan Neonatal Biobank IRBs prior to enrollment.The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported by R01 ES012933 and R21 ES021893 to DMR, the WSU-NIEHS Center (P30 ES020957), a pilot grant from the Institute for Population Sciences, Health Assessment, Administration, Services and Economics (INPHAASE) from Wayne State University and Henry Ford Medical Center to DM Ruden and MO Dereski, and a National Health and Nutrition Examination Survey), BLEEP (The Michigan Bloodspot Environmental Epidemiology Project) pilot grant from the University Research Corridor (URC) to DM Ruden. ICP-MS analyses were supported by NSF grant DUE-9952410 to K Hollacher. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.