ACE2 (angiotensin converting enzyme) polymorphisms and susceptibility of severe SARS- CoV-2 in subset of Pakistani population

Abstract

Science is digging for the varied presentation of COVID-19 patients exposed to the same risk factors, and medical conditions may be influenced by the presence of polymorphic genetic variants. This study investigated the link between ACE2 gene polymorphisms and the severity of SARS-Cov-2. This cross-sectional study recruited COVID-19 PCR-positive patients by consecutive sampling from Ziauddin Hospital from April to September 2020. DNA was extracted from whole blood, followed by gene amplification and Sanger’s sequencing. Most of the patients, 77: 53.8%, were serious. Males were higher (80; 55.9%) with age more than 50 years (106: 74.1%). We found 22 ACE2 SNPs rs2285666 SNP most prevalent with 49.2% CC, 45.2% TT, 4.8% CT heterozygosity, and 0.8% AA genotypes. Variants with multiple genotypes were also insignificantly associated with the severity of COVID-19 in the analysis of the dominant model. Only rs2285666 had a significant statistical link with gender (p-value 0.034, OR; 1.438, CI; 1.028-2.011) while rs768883316 with age groups (p-value 0.026, OR; 1.953, CI; 1.085-3.514). Haplotypes ATC of three polymorphisms (rs560997634, rs201159862, and rs751170930) commonly found in 120 (69.77%) and TTTGTAGTTAGTA haplotype consisting of 13 polymorphisms (rs756737634, rs146991645, rs1601703288, rs1927830489, rs1927831624, rs764947941, rs752242172, rs73195521, rs781378335, rs756597390, rs780478736, rs148006212, rs768583671) in 112 (90.32%) had statistically significant association with the severity having p=value 0.029 and 0.001 respectively. Males of old age and diabetics are found to have more severe COVID-19 infection in the current study. We also found that common ACE2 polymorphism rs2285666 influences the susceptibility of acquiring the severe SARS-CoV-2 infection.

Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population

“…Laboratory data from our patients and fndings from further research revealed that patients with severe and critical illness had considerably higher levels of CRP, Ddimer, and serum ferritin compared to mild/moderate cases (Tables S1 and S2) [27,28]. In addition, Gómez-Haranz et al…”

“…Laboratory data from our patients and findings from further research revealed that patients with severe and critical illness had considerably higher levels of CRP, D-dimer, and serum ferritin compared to mild/moderate cases (Tables S1 and S2 ) [ 27 , 28 ]. In addition, Gómez-Haranz et al reported significant correlations between case severity and different laboratory markers, including CRP, D-dimer, and ferritin levels [ 29 ].…”

“…Although many disease predictors have been reported, much research is still needed. Infection rates and outcomes could be dependent on the host's genetic background, especially those affecting the virus-cell interaction [ 27 ]. The main finding in this study was the higher prevalence of hetero and mutant genotypes of ACE-2 rs2285666 among severe (CT 26.7% and TT 53.3%) and critical (CT 33.3% and TT 53.3%) cases than that of controls (CT 15.0% and TT 10%).…”

“…These data were similar to recent data reported by Abdel Sattar et al in Egypt, who found that the genotypes CT and TT and the T allele were high predictors of severe illness [ 28 ]. In contrast, Sidhawani et al in Pakistan found that the TT genotype of rs2285666 was protective, while the CC genotype raised the likelihood of COVID-19 disease [ 27 ]. Çelik et al did not find any link between the rs2285666 polymorphism and disease severity [ 33 ].…”