title: Mitochondrial DNA and TFAM gene variation in early-onset myocardial infarction: evidence for an association to haplogroup H.
abstract: 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 °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.
authors.affiliation: Genética Molecular, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Palacín
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: María
authors.initials: M
authors.lastname: Martín
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Ana I
authors.initials: AI
authors.lastname: Corao
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.forename: Beatriz
authors.initials: B
authors.lastname: Díaz-Molina
authors.forename: Iñigo
authors.initials: I
authors.lastname: Lozano
authors.forename: Pablo
authors.initials: P
authors.lastname: Avanzas
authors.forename: César
authors.initials: C
authors.lastname: Morís
authors.forename: Julián R
authors.initials: JR
authors.lastname: Reguero
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.forename: Jorge
authors.initials: J
authors.lastname: Cannata-Andía
authors.forename: Alberto
authors.initials: A
authors.lastname: Batalla
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Camblor
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D012907:Smoking; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A