Impact of interleukin-1 gene polymorphisms on the severity of COVID-19

Abstract

The severity of Coronavirus Disease 2019 (COVID-19) has been closely linked to an exacerbated proinflammatory response and cytokine storm. Interleukin-1 (IL-1), a pivotal proinflammatory cytokine, plays a crucial role in the development of acute respiratory distress syndrome (ARDS) and multiorgan dysfunction. Single nucleotide polymorphisms within the IL-1 gene have been shown to modulate IL-1 cytokine levels. This study aimed to investigate the association of IL-1 gene polymorphisms (IL-1 + 3953C > T, IL-1β -511 T > C, and IL-1Ra) with the severity of COVID-19. Genotyping of IL-1 gene polymorphisms (IL-1 + 3953C > T, IL-1β -511 T > C) were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while IL-1Ra genotyping was done by Random Amplification of Polymorphic DNA (RAPD). PCR-RFLP data were validated through Sanger sequencing (SeqStudio Genetic Analyzer). Data analysis was carried out by SPSS-v21 and SHesis (online version). The frequency of the T allele of the IL-1 + 3953C > T polymorphism was found to be higher in mild cases as compared to severe cases, demonstrating a significant protective effect against COVID-19 severity (P = 0.001). However, no significant associations were observed for IL-1β -511 T > C and IL-1Ra polymorphisms (P > 0.05). In haplotype analysis (between IL-1 + 3953C > T, and IL-1β -511 T > C gene polymorphisms), individual with CT haplotype showed a higher risk of severity (OR = 1.8, P = 0.001), while individuals with TT haplotype showed significant protection against severity (P = 0.001). Our findings suggest that the T allele of IL-1β + 3953C > T polymorphism may confer protective effect against the severity of COVID-19.