Clinical and genetic analysis of essential hypertension with CYB gene m.15024G>A mutation.
10.3724/zdxbyxb-2023-0283
- Author:
Yunfan HE
1
;
Wenxu LI
2
;
Zhen LIU
2
;
Juanjuan ZHANG
2
;
Minxin GUAN
3
Author Information
1. School of Laboratory Medicine and Life Sciences, Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China. citronlake@163.com.
2. School of Laboratory Medicine and Life Sciences, Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
3. School of Laboratory Medicine and Life Sciences, Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China. gminxin88@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
Essential hypertension;
Gene mutation;
Maternal inheritance;
Mitochondrial DNA;
Mitochondrial dysfunction;
Respiratory chain
- MeSH:
Humans;
Middle Aged;
Aged;
Reactive Oxygen Species;
Essential Hypertension/genetics*;
Adenosine Triphosphate;
Cell Line;
Mutation
- From:
Journal of Zhejiang University. Medical sciences
2023;52(4):510-517
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:To explore the role of mitochondrial CYB 15024G>A mutation in the development of essential hypertension.
METHODS:Mitochondrial genome sequences of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with mitochondrial CYB 15024G>A mutation and its pedigree were analyzed. Lymphocytes derived from patient and family members were transformed into immortalized lymphoblastoid cell lines, and the levels of adenosine triphosphate (ATP), mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected.
RESULTS:The penetrance of this essential hypertension family was 42.9%, and the age of onset was 46-68 years old. Mitochondrial genome sequencing results showed that all maternal members carried a highly conserved mitochondrial CYB 15024G>A mutation. This mutation could affect the free energy of mitochondrial CYB for secondary and tertiary structure and protein folding, thereby changing its structural stability and the structure of the electron transfer function area around the mutation site. Compared with the control, the cell line carrying the mitochondrial CYB 15024G>A mutation showed significantly decreased levels of mitochondrial CYB, ATP and mitochondrial membrane potential, and increased levels of ROS (P<0.01).
CONCLUSIONS:Mitochondrial CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, leading to cell dysfunction, which suggests that the mutation may play a synergistic role in essential hypertension.
