Using MutPred derived mtDNA load scores to evaluate mtDNA variation in hypertension and diabetes in a two-population cohort：The SABPA study  

作　　者：Marianne Venter Leone Malan Etresia van Dyk Joanna L.Elson Francois H.van der Westhuizen Marianne Venter Leone Malan Etresia van Dyk Joanna L. Elson Francois H. van der Westhuizen(Human Metabolomics, North-West University, Potchefstroom 2531, South Africa Hypertension in Africa Research Team （HART）, North-West University, Potchefstroom 2531, South Africa Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom)

机构地区：[1]Human Metabolomics, North-West University, Potchefstroom 2531, South Africa [2]Hypertension in Africa Research Team (HART), North-West University, Potchefstroom 2531, South Africa [3]Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom

出　　处：《Journal of Genetics and Genomics》2017年第3期139-149,共11页遗传学报（英文版）

基　　金：the Faculty of Natural Sciences of the NorthWest University for contributing to funding and Thermo Fisher South Africa for providing additional technical resources to this study;partially funded by the South African National Research Foundation;Medical Research Council;ROCHE Diagnostics;North-West University,South Africa;as well as the Metabolic Syndrome Institute,France;funding support from the Royal Society and the National Research Foundation of South Africa, for the academic meeting at which the project was mapped out

摘　　要：Mitochondrial DNA（mt DNA） 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 Mut Pred Program.We apply this new methodology to investigate the possible role of mt DNA 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 mt DNA 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 mt DNA 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 mt DNA 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 mt DNA lineages, where the traditional haplogroup association method has been particularly likely to generate spurious results in the context of association with common complex disease.Mitochondrial DNA（mt DNA） 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 Mut Pred Program.We apply this new methodology to investigate the possible role of mt DNA 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 mt DNA 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 mt DNA 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 mt DNA 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 mt DNA lineages, where the traditional haplogroup association method has been particularly likely to generate spurious results in the context of association with common complex disease.

关 键 词：Mitochondrial DNA MutPred Mutational load HYPERTENSION Diabetes AFRICAN SABPA 

分 类 号：R544.1[医药卫生—心血管疾病] R587.1[医药卫生—内科学]