Abstract 3570: Common Mitochondrial Haplogroups Do Not Predict Risk of Ischemic Cardiovascular Disease, Mortality, or Longevity in the General Population

Abstract

Recently there have been numerous reports suggesting a role for mitochondrial haplogroups, defined by common polymorphisms in the mitochondrial genome, in the pathogenesis of common multifactorial disease such as ischemic cardiovascular disease, and in longevity. These studies have in common that they are all case-control studies with a very limited number of participants, and therefore are prone to selection bias and have very limited power. In the present study, we therefore tested the hypothesis that mitochondrial haplogroups predict risk of ischemic cardiovascular disease, mortality, and longevity in a large prospective study of a general population of Northern European descent. We genotyped 9,254 individuals from the Danish general population, The Copenhagen City Heart Study, for six polymorphisms (mt7028, mt10398, mt11719, mt12308, mt12612, mt15607) defining eight mitochondrial haplogroups, and determined the ability of these haplogroups to predict risk of ischemic cardiovascular disease, mortality, and longevity with, respectively, 25 and 11 years follow-up. Haplogroup frequencies were: H(45.9%), U(15.9%), T(9.9%), J(9.1), K(6.2%), V(4.5%), W/I(3.8%), and Z(3.5%). Multifactorially adjusted hazard ratios for hospitalization due to ischemic heart disease and ischemic cerebrovascular disease as a function of haplogroups were not significantly different from the most common haplogroup H. Furthermore, multifactorially adjusted hazard ratios for death of all causes as well as for major causes of death including ischemic cardiovascular disease as a function of haplogroups were also not significantly different from haplogroup H. Finally, on survival plots, longevity defined as percent surviving as a function of age by haplogroups did not differ when comparing each haplogroup with haplogroup H. In conclusion, in this large prospective study of a general population of Northern European descent mitochondrial haplogroups did not predict risk of ischemic cardiovascular disease, mortality, or longevity. Thus, our results suggest that mitochondrial haplogroups are not major predictors of ischemic cardiovascular disease, overall mortality, mortality from ischemic cardiovascular disease, or longevity in the general population.