Association of IFNAR2 rs2236757 and OAS3 rs10735079 Polymorphisms with Susceptibility to COVID-19 Infection and Severity in Palestine
Mohammad Abdelhafez, Abedelmajeed Nasereddin, Omar Abu Shamma, Rajaa Abed, Raghida Sinnokrot, Omar Marof, Tariq Heif, Zaid Erekat, Amer Al‐Jawabreh, Suheir Ereqat
Abstract
The clinical course and severity of COVID-19 vary among patients. This study aimed to investigate the potential correlation between the gene polymorphisms of the interferon receptor (IFNAR2) rs2236757 and oligoadenylate synthetase 3 (OAS3) rs10735079 with the risk of COVID-19 infection and its severity among Palestinian patients. The study was conducted between April and May 2021 on 154 participants who were divided into three groups: the control group (RT-PCR-negative, n = 52), the community cases group (RT-PCR-positive, n = 70), and the critically ill cases (ICU group; n = 32). The genotyping of the investigated polymorphisms was performed using amplicon-based next-generation sequencing. The genotypes distribution for the IFNAR2 rs2236757 was significantly different among the study groups (P = 0.001), while no statistically significant differences were found in the distribution of genotypes for the OAS3 rs10735079 (P = 0.091). Logistic regression analysis adjusted for possible confounding factors revealed a significant association between the risk allele rs2236757A and critical COVID-19 illness <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mfenced open="(" close=")" separators="|"> <a:mrow> <a:mi>P</a:mi> <a:mtext> </a:mtext> <a:mo><</a:mo> <a:mtext> </a:mtext> <a:mn>0.025</a:mn> </a:mrow> </a:mfenced> </a:math> . Among all patients, those who carried the rs2236757GA were more likely to have a sore throat (OR, 2.52 (95% CI 1.02–6.24); P = 0.011); the presence of the risk allele rs2236757A was associated with an increased risk to dyspnea (OR, 4.70 (95% CI 1.80-12.27); <f:math xmlns:f="http://www.w3.org/1998/Math/MathML" id="M2"> <f:mi>P</f:mi> <f:mtext> </f:mtext> <f:mo><</f:mo> <f:mtext> </f:mtext> <f:mn>0.001</f:mn> </f:math> ), while the rs10735079A carriers were less likely to develop muscle aches (OR, 0.34 (95% CI 0.13–0.88); P = 0.0248) and sore throat (OR, 0.17 (95% CI 0.05–0.55); <h:math xmlns:h="http://www.w3.org/1998/Math/MathML" id="M3"> <h:mi>P</h:mi> <h:mtext> </h:mtext> <h:mo><</h:mo> <h:mtext> </h:mtext> <h:mn>0.001</h:mn> </h:math> ). In conclusion, our results revealed that the rs2236757A variant was associated with critical COVID-19 illness and dyspnea, whereas the rs10735079A variant was protective for muscle aches and sore throat.