The genetic analysis of mitochondrial tRNAGln 4363 T > C mutation associated with essential hypertension in three Chinese Han pedigrees
1.Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, 325035; 2.Department of Emergency, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015; 3.Institute of Genetics, Zhejiang University, Hangzhou, 310058
YU Han1,GENG Junwei1,LIN Zhi1, et al. The genetic analysis of mitochondrial tRNAGln 4363 T > C mutation associated with essential hypertension in three Chinese Han pedigrees[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2015, 45(5): 313-.
Abstract：Objective: To analyze and evaluate the clinical, genetic and molecular characteristics of mtDNA in three Han Chinese pedigrees with essential hypertension and explore the role of tRNAGln 4363T>C mutation in the development of those maternally inherited essential hypertension. Method: Mitochondrial tRNA gene of 848 Chinese Han essential hypertension subjects and 254 control subjects were amplified with PCR. Members of 3 Chinese Han pedigrees with mitochondrial tRNAGln 4363T>C mutation underwent mitochondrial DNA genetic analysis and pedigree assessment. Result: Three essential hypertension subjects were found with tRNAGln 4363T>C mutation, and with variable severity and age-of-onset in hypertension among the three pedigrees. The percentage of this mutation was 0.35%. Twelve of 28 matrilineal relatives in these families exhibited the variable degree of hypertension at the age at onset of 27 to 64 years old and at the average of 44 years old, while none of the offspring at affected father had hypertension. Sequence analysis of complete mitochondrial genomes in 3 pedigrees showed that, in addition to the homoplasmic 4363T>C mutation, there were also 64 other mutations, and the mtDNA polymorphisms belonged to haplogroups Z3, Z3 and B4d, respectively. The tRNAGln 4363T was localized at immediately 3’end to the anticodon, corresponding to highly conserved adenine at position 38 of tRNAGln, the 4363C>T mutation might affect the high fidelity of recognition and the formation and stability of normal tRNA structure. Conclusion: The occurrence of the tRNAGln 4363T>C mutation in three genetically unrelated pedigrees affected by hypertension and the absence in 254 Chinese controls strongly indicate that this mutation is associated with essential hypertension. The homoplasmic form, late onset and incomplete penetrance of hypertension observed in those Chinese pedigrees suggest that tRNAGln 4363T>C mutation may be insufficient to produce a clinical phenotype, nuclear modifier gene (s) or environmental factor (s) may play a role in the phenotypic expression of essential hypertension related to tRNAGln 4363T>C mutation.
