Genetic determinants of angiotensin-converting enzyme levels (data from genome-wide studies)

Angiotensin converting enzyme (ACE) is a key enzyme of the renin-angiotensin- aldosterone system. It plays an important role in the early prognosis, diagnosis and treatment of diseases of the cardiovascular system (CVS), kidneys, and COVID‑19. Among the factors determining the ACE level, genetic factors play an important role. Understanding the role of specific genetic determinants associated with ACE levels is important, as these genetic determinants can be potentially used as markers of high ACE levels and, accordingly, markers of high risk of developing ACE-associated diseases.
Objective. To study the genetic determinants of ACE levels/activity using data genome-wide association search (GWAS).
Design and methods. A search for publications was performed in the GWAS catalog for the period from 2010 to 2024 using the keywords: angiotensin-converting enzyme, ACE.
Results. To date, 7 GWAS studies have been carried out, resulting in identification of 14 polymorphic loci associated with the level / activity of ACE. Among them, the largest number of SNPs is located in two regions of the genome — 17q23.3 (8 SNPs) and 9q34.2 (4 SNPs). Out of these, 79 % (11 SNPs) exhibit pronounced pleiotropic effects and are GWAS-significant in relation to indicators of lipid and carbohydrate metabolism, immune status, are associated with the functional activity of the liver and kidneys, blood pressure levels. These polymorphisms are associated with a number of diseases: CVS, COVID‑19, Alzheimer’s disease, venous thromboembolism. According to GWAS data, the most pronounced pleiotropic effects are exhibited by polymorphisms: rs507666, rs495828, rs8176746 of the ABO gene (9q34.2). According to genome-wide studies with all 14 loci associated with the level / activity of ACE, polymorphisms (more than 60 SNPs) are in linkage disequilibrium, which are associated with various numerous traits associated with lipid / carbohydrate metabolism, immune / vascular reactions, functional state of the liver and kidneys, intercellular interactions, coagulation / anticoagulation system, etc., as well as with cardiovascular diseases, type 2 diabetes mellitus, COVID‑19, etc.
Conclusions. The level / activity of ACE is genetically determined by polymorphisms of predominantly genome regions 17q23.3 and 9q34.2, which exhibit pronounced pleiotropic phenotypic effects.

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