Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients.

Sara H A Agwa,Aya M Abd Elsamee,Marwa Mostafa Kamel,Marwa Matboli,Hoda Ezz Elarab,Samia Abdo Girgis,Safa Matbouly Sayed,Hala Hafez,Fatma S E Ebeid,Hesham Elghazaly,Lina Sherif

doi:10.3390/genes12060830

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. Aim: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like–1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. Methods: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. Results: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. Conclusion: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.

Highlights

Most cases with severe acute respiratory syndrome coronavirus 2 (The SARS-CoV-2)infection demonstrate mild symptoms or are asymptomatic, but some cases may develop complications such as interstitial pneumonia and acute respiratory distress syndrome (ARDS), as seen in patients with advanced age and associated morbidities [1].The relation between single nucleotide polymorphism (SNP) and the immune response is called “immunogenetic profiling” [2]
We focused on cytokine polymorphisms at rs12979860 and rs17047200 loci, the allele frequencies reported in previous literatures and Discoidin domain receptor 1 (DDR1) gene polymorphism in COVID-19 positive patients to explore their relation to coronavirus infection severity and mortality
No statistically significant differences were found between COVID-19 positive patients and controls regarding age or sex with p = 0.252 and 0.201, respectively

Summary

Introduction

Most cases with severe acute respiratory syndrome coronavirus 2 (The SARS-CoV-2)infection demonstrate mild symptoms or are asymptomatic, but some cases may develop complications such as interstitial pneumonia and acute respiratory distress syndrome (ARDS), as seen in patients with advanced age and associated morbidities [1].The relation between SNPs and the immune response is called “immunogenetic profiling” [2]. Most cases with severe acute respiratory syndrome coronavirus 2 (The SARS-CoV-2). Infection demonstrate mild symptoms or are asymptomatic, but some cases may develop complications such as interstitial pneumonia and acute respiratory distress syndrome (ARDS), as seen in patients with advanced age and associated morbidities [1]. Genetic polymorphism plays an important role in cytokine function, which is crucial in the host inflammatory response [3]. Knowing that cytokines are crucial regulators of the individual response to infections [7], it is becoming clear that the immune system has an evident role in the cytokine storm as dangerous events in the disease known as ARDS [8,9]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses.

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