Implementing a new variant load model to investigate the role of mtDNA in oxidative stress and inflammation in a bi-ethnic cohort: the SABPA study

AbstractMitochondrial DNA (mtDNA) variation has been implicated in several common complex and degenerative diseases, including cardiovascular disease. Inflammation is seen as part of many of these conditions. Mitochondria feature in inflammatory pathways and it has been suggested that mtDNA variation or released mtDNA might be important in this phenomenon. To determine if mtDNA is involved in the mechanisms leading up to cardiovascular disease, we investigated the role of these variants in seven indicators of oxidative stress and inflammation. This study was done in participants of the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) cohort, a South African bi-ethnic cohort (N = 363). We applied a variant load hypothesis, which is an alternative approach to, and moves away from the classic haplogroup association approaches, to evaluate the cumulative effect of non-synonymous mtDNA variants on measurements of serum peroxides, nitric oxide metabolites, 8-hydroxy-deoxyguanosine, thiobar...