on May 5, 2008
Published online before print May 5, 2008, doi: 10.1161/CIRCULATIONAHA.107.756809
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Submitted on November 30, 2007
From the Departments of Clinical Biochemistry (M.B., A.T.-H.), and Clinical Genetics (M.S.), Rigshospitalet, Copenhagen University Hospital, Department of Clinical Biochemistry, Herlev University Hospital (B.G.N.), and the Copenhagen City Heart Study, Bispebjerg University Hospital (B.G.N., A.T.-H.), all Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. * To whom correspondence should be addressed. E-mail: at-h{at}rh.regionh.dk.
Background—Rare mutations in the mitochondrial genome may cause disease. Mitochondrial haplogroups defined by common polymorphisms have been associated with risk of disease and longevity. We tested the hypothesis that common haplogroups predict risk of ischemic cardiovascular disease, morbidity from other causes, mortality, and longevity in a general population of European descent. Methods and Results—We followed 9254 individuals from the Danish general population, in the Copenhagen City Heart Study, prospectively for risk of ischemic cardiovascular disease, morbidity from other causes, and mortality during 25 and 11 years, respectively. Haplogroup frequencies were as follows: 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%). Hazard ratios for hospitalization due to all cardiovascular disorders (haplogroup U: 1.0 [95% confidence interval{CI}, 0.9 to 1.1]; T: 0.9 [95% CI, 0.8 to 1.0]; J: 1.0 [95% CI, 0.9 to 1.1]; K: 1.0 [95% CI, 0.9 to 1.2]; V: 1.0 [95% CI, 0.9 to 1.2]; W/I: 0.8 [95% CI, 0.7 to 1.0]; Z: 1.0 [95% CI, 0.8 to 1.2]), ischemic heart disease (U: 0.9 [95% CI, 0.8 to 1.1]; T: 0.9 [95% CI, 0.7 to 1.0]; J: 1.1 [95% CI, 0.9 to 1.2]; K: 1.1 [95% CI, 0.9 to 1.3]; V: 1.1 [95% CI, 0.9 to 1.4]; W/I: 1.1 [95% CI, 0.8 to 1.4]; Z: 1.1 [95% CI, 0.8 to 1.4]), and ischemic cerebrovascular disease (U: 1.1 [95% CI, 0.9 to 1.4]; T: 0.9 [95% CI, 0.7 to 1.2]; J: 1.1 [95% CI, 0.9 to 1.4]; K: 1.0 [95% CI, 0.8 to 1.4]; V: 1.1 [95% CI, 0.8 to 1.5]; W/I: 0.8 [95% CI, 0.5 to 1.3]; Z: 0.9 [95% CI, 0.6 to 1.4]) did not differ from 1.0 for any haplogroup versus the most common haplogroup H. Results were similar for hospitalization due to infectious and parasitic diseases, respiratory infections, respiratory disorders, malignant neoplasms, digestive disorders, musculoskeletal disorders, neuropsychiatric disorders, and miscarriages. Likewise, hazard ratios for death from all causes were not different from 1.0 for any haplogroup versus haplogroup H (U: 1.0 [95% CI, 0.8 to 1.1]; T: 0.9 [95% CI, 0.8 to 1.1]; J: 0.9 [95% CI, 0.8 to 1.1]; K: 1.0 [95% CI, 0.8 to 1.2]; V: 1.1 [95% CI, 0.9 to 1.3]; W/I: 0.8 [95% CI, 0.7 to 1.1]; Z: 0.9 [95% CI, 0.7 to 1.2]). Finally, after stratification by major causes of death, hazard ratios remained insignificant. Conclusions—Our results do not support an association of mitochondrial haplogroups with risk of ischemic cardiovascular disease, morbidity from other causes, mortality, or longevity in a large general population of European descent.
Accepted on February 22, 2008
Mitochondrial Haplogroups. Ischemic Cardiovascular Disease, Other Diseases, Mortality, and Longevity in the General Population
Marianne Benn MD, PhD,
Key words: cardiovascular diseases • cerebrovascular disorders • genetics • morbidity • mortality
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