Affiliations: Genética Molecular, Hospital Central Asturias,
Oviedo, Spain | Cardiología-Fundación Asturcor, Hospital
Central Asturias, Oviedo, Spain | Charité – Universitätsmedizin
Berlin/Kardiologie am Campus Buch & Virchow-Klinikum,
Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany | Cellular Biology in Renal Diseases Laboratory,
Fundación Jiménez Díaz and Universidad Autónoma de
Madrid, Madrid, Spain | Red de Investigación Renal-REDINREN,
Spain | Instituto Reina Sofía de Investigación
Nefrológica, Spain
Note: [] a
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.
