Journal
MITOCHONDRION
Volume 11, Issue 1, Pages 176-181Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2010.09.004
Keywords
Atherosclerosis; Myocardial infarction; Mitochondria; Haplogroups; Mitochondrial transcription factor
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Funding
- Spanish Fondo de Investigaciones Sanitarias-Fondos FEDER European Union [FIS-06/0214, 09-00172]
- Red de Investigacion Renal-REDINREN [RD06/0016]
- FICYT
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The main objective of this research was to define the association between common mitochondrial DNA (mtDNA) polymorphisms and mitochondrial transcription A gene (TFAM) variants and myocardial infarction (MI) in patients with atherosclerotic diseased vessels. Ten mitochondrial polymorphisms that defined the nine common European haplogroups were genotyped in 500 male patients with early onset MI (<55 years) and at least one atherosclerotic coronary vessel (angiographically confirmed), and 500 healthy controls. In addition, we searched for DNA variants in the coding region of the TFAM gene and compared patients and controls for the allele and genotype frequencies. Early onset MI was strongly associated with male gender and tobacco smoking in our population. MtDNA haplogroup H (defined by allele 7028 degrees C) was significantly more frequent in a first group of patients (n=250) compared to controls (n=300), and the association was confirmed in a second group of only smokers (250 patients and 200 controls). For total patients and controls, we obtained a p = 0.002 (OR = 1.50; 95% CI = 1.17-1.92) for H vs. the other haplogroups. We found four common TFAM polymorphisms, with allele/genotype frequencies that did not differ between patients and controls. In conclusion, mitochondrial haplogroup H was associated with early onset MI in male smokers. Our work supported a role for the mtDNA variation in the risk for atherosclerosis and ischemic associated events, likely due to differences in mitochondrial function and reactive oxygen production between the different haplogroups. (C) 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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