Hala Almajzoub
Hala Almajzoub1, Hussam Al-Bardan2, Raghad Almajzoub3, Shaden Haddad1
1 Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University, Syria.
2 Department of Pulmonary Medicine, AL Mouwasat University Hospital, Damascus University, Syria.
3 Faculty of Medicine, Damascus University, Syria.
Frequency of ACE Insertion/Deletion Polymorphism and Its Influence on COVID-19 Severity and Mortality in Syrian Patients
Background:
The COVID-19 pandemic, caused by SARS-CoV-2, has demonstrated highly variable clinical outcomes ranging from asymptomatic infection to severe pneumonia and death. Host genetic factors are increasingly recognized as key determinants of disease susceptibility and progression. Among these, the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been extensively hypothesized to influence COVID-19 severity due to its role in modulating ACE enzyme levels and disrupting the renin-angiotensin-aldosterone system (RAAS) balance. However, findings across global populations remain contradictory, and Syrian patients have been largely underrepresented in such genetic association studies.
Objectives:
This study aimed to compare the frequency of the ACE I/D polymorphism between non-severe and severe Syrian COVID-19 patients, and to evaluate its association with mortality among hospitalized severe cases.
Methods:
A total of 58 RT-PCR-confirmed Syrian COVID-19 patients were enrolled, including 28 non-severe and 30 severe cases. Genotyping of the ACE I/D polymorphism (rs4646994) was performed using two independent conventional PCR protocols to prevent misclassification. Data were analyzed using Chi-square and Fisher’s exact tests, with Hardy-Weinberg equilibrium assessed for each group.
Results:
The ID genotype was the most frequent in both groups (64.3% in non-severe, 70% in severe). The DD genotype was observed in 35.7% of non-severe and 20% of severe patients, while the II genotype appeared exclusively in the severe group (10%). No statistically significant association was found between the ACE I/D polymorphism and COVID-19 severity (p=0.148) or mortality among hospitalized patients (p=0.179). As anticipated, older age, male sex, diabetes, and hypertension were significantly linked to severe disease (p<0.05 for all).
Conclusion:
Our findings do not support a major role for the ACE I/D polymorphism in determining severe outcomes or mortality in Syrian COVID-19 patients. These results underscore the need for larger, multi-center studies incorporating other RAS-related genetic variants to clarify the clinical relevance of this polymorphism in our population.
Keywords:
COVID-19; ACE I/D polymorphism; disease severity; mortality; Syrian population