The Frequency of Angiotensin Converting Enzyme (ACE) Gene Insertion/Deletion (I/D) Polymorphism in Healthy Syrians and Thrombosis and Hypertensive Patients: a Case-Control Study

Abstract

Background: Angiotensin-converting enzyme (ACE) is a critical co-regulator of the kallikrein-kinin (KKS) and renin-angiotensin-aldosterone (RAS) systems. The gene encoding this enzyme is subject to polymorphisms, the most important of which is the insertion/deletion (I/D) polymorphism, which affects the serum and tissue levels of ACE, its structure and functions. The D polymorphism is attributed to it involvement in the pathophysiology of several diseases.

Objective: This study aimed to investigate the frequency of the rs4646994 (I/D) polymorphism in a Syrian cohort of healthy individuals in comparison with patients with high blood pressure and/or venous thrombosis to assess the assumed association between the I allele and these disease states.

Methods: In this case-control study, we included healthy individuals (control arms) and patients with hypertension and/or thrombosis from the governorates of Damascus, Rural Damascus, and Homs. We extracted genomic DNA and performed PCR using primer pairs specific for the region containing the ACE I/D gene polymorphism. Alleles and genotypes were identified based on the lengths of the amplicons after migration on an agarose gel.

Results: One hundred forty-six individuals met the inclusion criteria; their ages ranged from 21-86 years, with an arithmetic mean (±standard deviation) of 49.68 (±17.56) years, and a majority (60.69%) of males. The total number of alleles was 292 alleles, with the D allele being dominant (64.73%), compared to a percentage did not exceed 35.27% for the I allele. The study subjects were distributed according to the genotypes to: II (13.01%), ID (44.52%), DD (42.47%). Thus, the percentage of carriers of at least one copy of the deletion allele (ID+DD) was 86.99%. The frequency of the D allele was 62.50% in patients with venous thrombosis (n= 20) and 66.67% in patients with arterial hypertension (n= 27), compared to 64.29% in healthy controls (p>> 0.05).

Conclusions: This study reveals a relatively high prevalence of the deletion allele D. The percentage of carriers of at least one copy of the deletion allele (ID+DD) was comparable to prevalence rates reported in Africa (86.4 (%[83.6-%94.7%] and the Middle East (84.5 (%[78.3-%89.8%]. The prevalence of the D allele was almost identical in healthy individuals and patients with arterial hypertension and venous thrombosis, which may suggest other reasons for predisposition to these diseases in Syrians.