Mitochondrial DNA Copy Number Dynamics from Birth through Adolescence in a Population of Dominican and African American Children

Abstract

Background: Mitochondria are vital for cellular energy production, metabolism, and signaling; however, they are uniquely susceptible to damage from environmental toxicants. Mitochondrial DNA copy number (mtDNAcn) is a widely used biomarker in human population studies and is associated with several exposures, including air pollution and metals. Yet, little is known about the dynamics of mtDNAcn throughout childhood and its longitudinal associations with key population characteristics. Our objective was to profile mtDNAcn from birth through adolescence to better inform future environmental health research. Methods: Data were collected from a cohort of mother-child pairs from New York City recruited 1998-2006 and followed through 18 years. Using duplexed qRT-PCR we quantified mtDNAcn relative to nuclear DNA from 662 participants using blood collected from the umbilical cord (n=450), children aged 5-7 (n=510), and adolescents aged 15-18 (n=278). We examined mtDNAcn across childhood with linear mixed-effects models (LMM) and latent class growth models (LGCM). We then examined associations with key population characteristics (maternal lifestyle during pregnancy and birth outcomes). Results: Relative mtDNAcn was lowest at birth (mean ± SD: 0.67 ± 0.35) and increased in childhood (1.24 ± 0.50) then slightly declined in adolescence (1.13 ± 0.44). MtDNAcn values across visits were moderately correlated (r=0.32-0.44). LGCM identified two trajectories of mtDNAcn: a high group (n=615) and a smaller low group (n=47). We observed no differences in mtDNAcn by sex or by race/ethnicity. In LMMs, longitudinal mtDNAcn was positively associated with prenatal environmental tobacco smoke exposure but negatively associated with maternal education and maternal receipt of public assistance at birth. No associations were observed with child birth outcomes. Conclusions: MtDNAcn levels were dynamic through childhood and are associated with prenatal factors. These results underscore the need for the investigation of mtDNAcn dynamics and predictors for environmental health research. Keywords: Biomarkers, mitochondria, mtDNA, children’s environmental health