title: Mitochondrial transcription factors TFA, TFB1 and TFB2: a search for DNA variants/haplotypes and the risk of cardiac hypertrophy.
abstract: Mitochondrial transcription factors mtTFA, mtTFB1 and mtTFB2 are required for the replication of mitochondrial DNA (mtDNA), regulating the number of mtDNA copies. Mice with a mtTFA deletion showed a reduced number of mtDNA copies, a reduction in respiratory chain activity, and a characteristic dilated cardiomyopathy. DNA variants in these genes could be involved in the risk for cardiac hypertrophy (HCM). We determined the variation in the TFAM, TFB1M, and TFB2M genes (using SSCA, DHPLC, and direct sequencing) in a total of 200 HCM-patients from Spain and Germany, and in 250 healthy controls. We found several common polymorphisms that defined haplotype blocks in these genes, with frequencies that did not differ between patients and controls. We also found four novel variants in patients which were absent in the controls: -91 C > A (5'-UTR) and Ala105 > Thr in TFAM, and Thr211 > Ala and Arg256 > Lys in TFB1M. The three missense changes were in highly conserved amino acids, and could be involved in HCM-risk. In conclusion, common variants in the mitochondrial transcription factors were not associated with the risk for HCM. However, rare DNA variants (putative mutations) could be involved in the pathogenesis of HCM in a reduced number of cases.
authors.affiliation: Genética Molecular, Hospital Central Asturias, Oviedo, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alonso-Montes
authors.forename: Mónica G
authors.initials: MG
authors.lastname: Castro
authors.forename: Julián R
authors.initials: JR
authors.lastname: Reguero
authors.forename: Andreas
authors.initials: A
authors.lastname: Perrot
authors.forename: Cemil
authors.initials: C
authors.lastname: Ozcelik
authors.forename: Christian
authors.initials: C
authors.lastname: Geier
authors.forename: Maximilian G
authors.initials: MG
authors.lastname: Posch
authors.forename: César
authors.initials: C
authors.lastname: Morís
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D024101:Mitochondrial Proteins; C499631:TFAM protein, human; C499632:TFB1M protein, human; D014157:Transcription Factors; D008780:Methyltransferases; C462443:TFB2M protein, human