Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients

Abstract

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID19 patients (OR: 2.48, 95% CI: 1.331–4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms

“…In India, Verma et al genotyped ACE1 I/D polymorphisms using RT-PCR with a sample of 269 COVID-19 patients and then performed a statistical analysis of the association between COVID-19 symptoms and ACE1 I / D polymorphism [50]. They found that the frequency of the ACE1 DD genotype and D allele was significantly higher in patients with severe COVID-19.…”

Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

“…Age and sex, indeed, represent non-genetic factors that primarily influence disease severity [69], but not exclusively. Verma et al [70] reported a correlation between ACE I/D (OR = 2.5. Table 1) polymorphism and a cluster of patients affected by diabetes mellitus and high blood pressure.…”

Host polymorphisms and COVID-19 infection

“…Viral infection may lead to further suppression of ACE2 function and cause ACE1/ACE2 imbalance responsible for RAAS over-activation and pulmonary shutdown [54] . The ACE1/ACE2 imbalance predicts that COVID-19 patients with the D allele of ACE1, especially the DD genotype, will have a more severe course of the disease, as seen in SARS patients with an ACE1 DD genotype [58] , [59] . An Italian study showed an inverse correlation between the I/I polymorphism and COVID-19-related deaths [60] , whereas others investigated the link between ACE I/D polymorphism and acute pulmonary embolism in COVID-19 pneumonia.…”