Molecular characterization of a pedigree carrying the hypertension-associated mitochondrial tRNA(Gln) T4363C mutation

Mitochondrial DNA mutations have been reported to be associated with essential hypertension. The present study reported the clinical and molecular features of a Chinese pedigree with maternally inherited hypertension. A total of 6 matrilineal relatives in this pedigree presented with variable degrees of hypertension; the age of onset ranged between 39 and 63 years, and the average age of onset was 53 years. Analysis of the mitochondrial genome in members of this family demonstrated the occurrence of a homoplasmic T4363C mutation in the transfer (t)RNA(Gln) gene and 25 genetic polymorphisms belonging to mitochondrial haplogroup B4. Notably, the T4363C mutation was localized at the anticodon stem of tRNA(Gln), which is highly conserved across various species (conventional position 38). To determine its potential pathogenicity, RNA Fold software was used to predict the secondary structure of tRNA(Gln) with and without this mutation. The results indicated that the T4363C mutation induced a significant alteration in the secondary structure of tRNA(Gln), and may reduce the steady-state levels of tRNA(Gln). Furthermore, matrilineal relatives carrying the T4363C mutation exhibited different age of onset and variable degrees of blood pressure, thus indicating that the T4363C mutation itself was insufficient to produce the clinical phenotype. Therefore, other modified factors, including environmental factors, and nuclear gene and epigenetic modifications, may be involved in the pathogenesis of hypertension. In conclusion, the present study provided valuable information regarding the association between tRNA mutations and hypertension.