A novel GJA5 variant associated with increased risk of essential hypertension.

Autor:	Wang J; Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine Shanghai 200120, China., Wang XC; Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine Shanghai 200120, China., Gu ZH; Sanlin Community Health Service Center Pudong New District, Shanghai 200124, China., Ren GW; Sanlin Community Health Service Center Pudong New District, Shanghai 200124, China., Zhao XH; Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine Shanghai 200120, China., Qu XK; Department of Cardiology, Huadong Hospital, Fudan University Shanghai 200040, China., Xu YJ; Department of Cardiology, Shanghai Fifth People's Hospital, Fudan University Shanghai 200240, China., Yang YQ; Department of Cardiology, Shanghai Fifth People's Hospital, Fudan University Shanghai 200240, China.; Department of Cardiovascular Research Laboratory, Shanghai Fifth People's Hospital, Fudan University Shanghai 200240, China.; Department of Central Laboratory, Shanghai Fifth People's Hospital, Fudan University Shanghai 200240, China.
Jazyk:	angličtina
Zdroj:	American journal of translational research [Am J Transl Res] 2023 Feb 15; Vol. 15 (2), pp. 1259-1270. Date of Electronic Publication: 2023 Feb 15 (Print Publication: 2023).
Abstrakt:	Objectives: Gap junction protein alpha 5 (GJA5), also termed connexin 40 (Cx40), exerts a pivotal role in the mediation of vascular wall tone and two closely-linked polymorphisms in the GJA5 promoter (-44G>A and +71A>G) have been associated with enhanced susceptibility to essential hypertension (EH) in men. The present investigation aimed to ascertain whether a novel common polymorphism within the upstream regulatory region of GJA5 (transcript 1B), -26A>G (rs10465885), confers an increased risk of EH. Methods: For this investigation, 380 unrelated patients with EH and 396 unrelated normotensive individuals employed as control persons were enrolled from the Chinese Han-ethnicity population, and their GJA5 genotypes and plasma renin concentrations were determined by Sanger sequencing and an automated chemiluminescent immunoassay, respectively. The functional effect of the GJA5 variant was explored in cultured murine cardiomyocytes by dual-light reporter gene analysis. Results: The GJA5 variant conferred a significantly increased risk for EH (OR: 2.156; 95% CL: 1.661-2.797, P < 0.0001), and significantly increased plasma renin levels were measured in patients with EH in comparison with control individuals (46.3±7.2 vs 37.4±6.9, P < 0.0001). A promoter-luciferase analysis revealed significantly diminished activity of the promoter harboring the minor allele for this variation in comparison with its wild-type counterpart (165.67±16.85 vs 61.53±8.67, P = 0.0007). Conclusions: These findings indicate that the novel variant upstream of the GJA5 gene (-26A>G) confers a significantly increased vulnerability of EH in humans, suggesting potential clinical implications for precisive prophylaxis and treatment of EH. Competing Interests: None. (AJTR Copyright © 2023.)
Databáze:	MEDLINE
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