Association of mitochondrial DNA haplogroup, oxidative DNA damage and inflammatory markers in middle-aged adults

Previous literature suggests that African American adults have higher levels of systemic oxidative stress than White adults. Mitochondrial DNA (mtDNA) variants can be traced to geographic origins of populations and classified into haplogroups. Emerging evidence indicates that mtDNA haplogroup may affect cellular stress responses such as the response to irradiation or oxidative stress. However, little is known about whether mtDNA haplogroup influences systemic baseline or induced levels of oxidative DNA damage.

We determined mtDNA haplogroup (African American or European) in 104 middle-aged adults living above and below poverty to investigate the association of mtDNA haplogroup and inflammatory markers with baseline and H₂O₂-induced DNA damage in peripheral blood mononuclear cells. DNA damage was measured using a high-throughput CometChip assay. Several inflammatory markers were measured in serum. Linear regression examined if variables were related to DNA damage in interactions or independently.

mtDNA haplogroup alone did not influence levels of baseline or H₂O₂-induced DNA damage. However, baseline and H₂O₂-induced DNA damage were associated with poverty, sex, age, and markers of inflammation. Baseline DNA damage was related to IL-6 levels differentially based on poverty status. Baseline DNA damage was inversely associated with levels of IL-8. Men showed overall higher levels of H₂O₂-induced DNA damage. H₂O₂-induced DNA damage was also related to IL-6 levels but differentially based on age. mtDNA haplogroup did affect both baseline and H₂O₂-induced DNA damage through differential effects on two markers of inflammation.

These data suggest that mtDNA haplogroup plays an indirect role in the cellular response to endogenous and exogenous oxidative stress. Sex and age may also contribute to levels of inflammation in the DNA damage response. Finally, the social determinant of health poverty status, appears to play a role in interactions with inflammatory markers for baseline DNA damage at mid-life.