title: Using MutPred derived mtDNA load scores to evaluate mtDNA variation in hypertension and diabetes in a two-population cohort: The SABPA study.
abstract: Mitochondrial DNA (mtDNA) variation has been implicated in many common complex diseases, but inconsistent and contradicting results are common. Here we introduce a novel mutational load hypothesis, which also considers the collective effect of mainly rare variants, utilising the MutPred Program. We apply this new methodology to investigate the possible role of mtDNA in two cardiovascular disease (CVD) phenotypes (hypertension and hyperglycaemia), within a two-population cohort (n = 363; mean age 45 ± 9 yrs). Very few studies have looked at African mtDNA variation in the context of complex disease, and none using complete sequence data in a well-phenotyped cohort. As such, our study will also extend our knowledge of African mtDNA variation, with complete sequences of Southern Africans being especially under-represented. The cohort showed prevalence rates for hypertension (58.6%) and prediabetes (44.8%). We could not identify a statistically significant role for mtDNA variation in association with hypertension or hyperglycaemia in our cohort. However, we are of the opinion that the method described will find wide application in the field, being especially useful for cohorts from multiple locations or with a variety of mtDNA lineages, where the traditional haplogroup association method has been particularly likely to generate spurious results in the context of association with common complex disease.
authors.affiliation: Human Metabolomics, North-West University, Potchefstroom 2531, South Africa.
authors.forename: Marianne
authors.initials: M
authors.lastname: Venter
authors.affiliation: Hypertension in Africa Research Team (HART), North-West University, Potchefstroom 2531, South Africa.
authors.forename: Leone
authors.initials: L
authors.lastname: Malan
authors.affiliation: Human Metabolomics, North-West University, Potchefstroom 2531, South Africa.
authors.forename: Etresia
authors.initials: E
authors.lastname: van Dyk
authors.affiliation: Human Metabolomics, North-West University, Potchefstroom 2531, South Africa; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom. Electronic address: j.l.elson@ncl.ac.uk.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Elson
authors.affiliation: Human Metabolomics, North-West University, Potchefstroom 2531, South Africa.
authors.forename: Francois H
authors.initials: FH
authors.lastname: van der Westhuizen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D059645:Mutation Rate; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial
keywords: African; Diabetes; Hypertension; Mitochondrial DNA; MutPred; Mutational load; SABPA