The role of ACE1 I/D and ACE2 polymorphism in the outcome of Iranian COVID-19 patients: A case-control study

Abstract

Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity.Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples.Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19.Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population.

The ACE rs1799752 Variant Is Associated with COVID-19 Severity but Is Independent of Serum ACE Activity in Hospitalized and Recovered Patients

“…A recent meta-analysis, including 11 studies with 950 patients with severe COVID-19, and 1573 patients with non-severe disease, reported that the DD genotype was related to COVID-19 severity through different models [22]. This finding agrees with our study and other reports in diverse populations [19,20,23] as well as another meta-analysis [24], which highlights the relevance of the RAS system, mainly the ACE gene, in the severity of COVID-19 and other pulmonary diseases. According to our findings, the DD genotype confers a risk of IMV requirement; meanwhile, the heterozygous genotype (ID) shows a decreased risk of requiring the procedure.…”

The Effect of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on the Severity and Death Rate of COVID-19 in Iranian Patients

“…Although there was no signi cant association between genotypes and the outcome of disease, remarkably higher percentage of II genotype in dead cases (15%) than that in survived cases (4%), as well as noteworthy drop in the OS curve of patients carrying this genotype can be a clue for future studies with larger statistical sample size to verify the impact of II genotype on reducing survival and increasing death. These ndings are also consistent with another recent study on Iranian population in which the presence of I allele (II and ID) signi cantly increased the risk of intubation and the mortality rate in COVID-19 patients (Faridzadeh et al 2022). Moreover, they reported a signi cantly lower frequency of DD genotype in intubated patients, which can optimistically support our non-signi cant results based on approximately 8% reduction of DD genotype in dead cases (55%) compared to survived cases (around 63%).…”

HLA alleles associated with COVID-19 susceptibility and severity in different populations: a systematic review

“…These contradictory findings warrant further large, and reproducible studies to decipher any possible genetic predisposition underlying susceptibility to SARS-COV-2 and disease progression and host immune response. In this regard, many studies assessed the impact of polymorphisms in the genes that encode crucial renin-angiotensin system components which are ACE or ACE2 on the susceptibility, severity, and clinical outcomes of the COVID-19 infection, exploring the hypothesis that individuals with ACE polymorphisms may have a more severe disease course in response to infection with SARS-CoV-2 [40][41][42][43][44]. Again, findings are controversial.…”