Clinical and genetic analysis of essential hypertension with MTCYB gene 15024G>A mutation

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Aug 9:1-9. doi: 10.3724/zdxbyxb-2023-0283. Online ahead of print.


OBJECTIVES: To explore the role of MT-CYB 15024G>A mutation in the development of essential hypertension.

METHODS: The mitochondrial genome sequencing results of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with MT-CYB m.15024 G>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 ATP, mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected.

RESULTS: The penetrance of this essential hypertension family (WHP121) 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 MT-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 MT-CYB 15024G>A mutation showed significantly decreased levels of mitochondrial ATP and mitochondrial membrane potential, and the increased levels of ROS (P<0.01).

CONCLUSIONS: MT-CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, further leading to cell dysfunction, which indicates that this mutation may play a synergistic role in essential hypertension.

PMID:37562966 | DOI:10.3724/zdxbyxb-2023-0283