A mitochondrial mutation A4401G is involved in the pathogenesis of left ventricular hypertrophy in Chinese hypertensives.

摘要

The left ventricular hypertrophy (LVH) is one of the most important organ damage targets in hypertension. Despite the involvement of multiple factors, the genetic factors have been shown to have an important function in the pathogenesis of LVH. The aim of our study was to evaluate the role of mitochondria in LVH for Chinese hypertensives. A systematic and extended mutational screening for the mitochondrial genome has been initiated in a large cohort of Chinese population by the Geriatric Cardiology Clinic at the Chinese PLA General Hospital, Beijing, China. Specific mutations within the mitochondria were further evaluated. Changes of total RNAs (tRNAs) were measured by northern blotting using nonradioactive digoxigenin (DIG)-labeled oligodeoxynucleotides specific for each RNA. Rates of oxygen consumption in intact cells were determined with av YSI 5300 oxygraph. Sequence analysis of mitochondrial DNA in one Chinese pedigree identified a novel A-G transition at position 4401 (A4401G) at the junction of tRNA(Met) and tRNA(Gln). The noncoding region mutation appeared to affect the processing of precursors in these mitochondrial tRNAs. The reduction in the rate of respiration and marked decreases in the steady-state levels of tRNA(Met) and tRNA(Gln) were detected in the cells carrying this mutation. The novel mutation was absent in 270 Chinese control patients. In conclusion, the noncoding mitochondrial sequence alteration (A4401G) alters mitochondrial function, implicating this mutation in the pathogenesis of LVH in Chinese hypertensives.