Mitochondrial haplogroups associated with end-stage heart failure and coronary allograft vasculopathy in heart transplant patients.

AIMS: Mitochondrial haplogroups are known to influence individual predisposition to a wide spectrum of metabolic and degenerative diseases, including ischaemic cardiovascular diseases. We have examined the influence of the mitochondrial DNA (mtDNA) background on the development of human end-stage heart failure (HF) in patients undergoing heart transplantation. The influence of mtDNA haplogroups on the incidence of transplant-related complications, mainly cardiac allograft vasculopathy (CAV), and on post-transplant survival was also studied. METHODS AND RESULTS: The most common mitochondrial haplogroups in European populations were genotyped in 450 heart transplant recipients, 248 heart transplant donors, and 206 healthy controls. Mitochondrial haplogroups were determined by PCR amplification of short mtDNA fragments, followed by restriction fragment length polymorphism analysis. After adjustment for age and sex the frequency of haplogroup H was significantly higher in heart transplant recipients than in controls [OR: 1.86 (95% confidence intervals, CI: 1.27-2.74), P= 0.014], and in heart donors [OR: 1.47 (95% CI: 0.99-2.19), P= 0.032]. Likewise, haplogroup Uk was found significantly more frequently among CAV patients than in non-CAV heart allograft recipients [OR: 4.1 (95% CI: 1.51-11.42), P= 0.042]. Finally, heart donor haplogroups had no influence on the morbidity or mortality after heart transplantation. CONCLUSIONS: Mitochondrial haplogroups behave like risk factors for the progress to end-stage HF in a Spanish cardiac transplant population. Mitochondrial DNA variants may have some influence on the appearance of cardiac transplant complications.

Mitochondrial tRNA valine as a recurrent target for mutations involved in mitochondrial cardiomyopathies.

The aim of this study was to identify the genetic defect in two patients having cardiac dysfunction accompanied by neurological symptoms, and in one case MRI evidence of cortical and cerebellar atrophy with hyperintensities in the basal ganglia. Muscle biopsies from each patient revealed single and combined mitochondrial respiratory chain deficiency. The complete mtDNA sequencing of both patients revealed two transitions in the mitochondrial tRNA(Val) gene (MT-TV) (m.1628C>T in Patient 1, and m.1644G>A in Patient 2). The functional and molecular analyses reported here suggest that the MT-TV gene should be routinely considered in the diagnosis of mitochondrial cardiomyopathies.