Clinical and genetic analysis of essential hypertension with mitochondrial tRNAMet 4435A>G and YARS2 mutation
10.3724/zdxbyxb-2023-0571
- VernacularTitle:携带线粒体tRNAMet 4435A>G和核基因YARS2突变的原发性高血压家系遗传学分析
- Author:
Meili GUO
1
;
Yunfan HE
;
Ade CHEN
;
Zaishou ZHUANG
;
Xiaoyong PAN
;
Minxin GUAN
Author Information
1. 苍南县人民医院检验科,浙江 温州 325800
- Keywords:
Essential hypertension;
Mitochondrial DNA;
Gene mutation;
Respiratory chain;
Mitochondrial dysfunction;
Maternal inheritance
- From:
Journal of Zhejiang University. Medical sciences
2024;53(2):184-193
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of m.4435A>G and YARS2 c.572G>T(p.G191V)mutations in the development of essential hypertension.Methods:A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data.Clinical data were collected,and a molecular genetic study was conducted in the proband and his family members.Peripheral venous blood was collected,and immortalized lymphocyte lines constructed.The mitochondrial transfer RNA(tRNA),mitochondrial protein,adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),and reactive oxygen species(ROS)in the constructed lymphocyte cell lines were measured.Results:Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation.The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability,which may influence the anticodon ring structure.Compared with the control group,the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis,mitochondrial protein expression,ATP production and MMP levels,as well as increased ROS levels(all P<0.05).Conclusion:The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction,indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.
