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Disease Markers
Volume 25, Issue 3, Pages 131-139

Mitochondrial Transcription Factors TFA, TFB1 and TFB2: A Search for DNA Variants/Haplotypes and the Risk of Cardiac Hypertrophy

Cristina Alonso-Montes,1 Mónica G. Castro,1 Julián R. Reguero,2 Andreas Perrot,3 Cemil Özcelik,3 Christian Geier,3 Maximilian G. Posch,3 César Morís,2 Victoria Alvarez,1 Marta Ruiz-Ortega,4,5 and Eliecer Coto1,5,6

1Genética Molecular, Hospital Central Asturias, Oviedo, Spain
2Cardiología-Fundación Asturcor, Hospital Central Asturias, Oviedo, Spain
3Charité – Universitätsmedizin Berlin/Kardiologie am Campus Buch & Virchow-Klinikum, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany
4Cellular Biology in Renal Diseases Laboratory, Fundación Jiménez Díaz and Universidad Autónoma de Madrid, Madrid, Spain
5Red de Investigación Renal-REDINREN, Spain
6Instituto Reina Sofía de Investigación Nefrológica, Spain

Received 5 December 2008; Accepted 5 December 2008

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.