Abstract

African-origin populations are more susceptible to diabetes and other age-related diseases compared to European-origin populations, but mechanisms for the differential susceptibility remain unknown. Human mitochondrial (mt) DNA haplogroups are maternally inherited ancient polymorphisms representing different geographic origins of populations. Haplogroups are defined by accumulations of single nucleotide polymorphisms (SNPs), some of which cause changes in amino acids and rates of mtDNA replication and transcription. Several studies have shown that age-related diseases and their complications can be linked to mtDNA haplogroup subsets. Previous studies report that transmitochondrial cybrids (cytoplasmic hybrids), which contain identical nuclei but either European-origin (H) or African-origin (L) haplogroup mtDNA, have significantly different bioenergetic profiles, production levels of reactive oxygen species, and expression levels for complement, inflammation and apoptosis genes, thus suggesting that major biological pathways can be modulated by mtDNA. Using GeneChip arrays and Q-PCR, we show that African-origin L cybrids show significantly different expression levels for three Wnt pathway genes (DKK3, SFRP1, and KREMEN1) and three diabetes-related genes (RPS6KA4, ADAMTS9, and VEGFA) compared to European-origin H cybrids. Our current findings, along with others, support the hypothesis that an individual’s mtDNA can modulate the expression of important Wnt signaling and diabetes-related genes, which may contribute to the racial/ethnic disparities associated with diabetes and other age-related diseases.

Authors and Affiliations