Interleukin-1 genetic polymorphisms in knee osteoarthritis: What do we know? A meta-analysis and systematic review

Abstract

Purpose Interleukin-1 is the main proinflammatory cytokine in osteoarthritis (OA). Several single-nucleotide polymorphisms (SNPs) within the IL-1 gene cluster (IL-1β, IL-1R1, and IL-1RN) have been determined, but their associations with knee OA remain poorly understood. The present study aimed to identify the associations between IL-1 SNPs and knee osteoarthritis. Methods This meta-analysis and systematic review included all comparative studies published in the MEDLINE/PubMed, Embase, Google Scholar, and Cochrane Library databases. We performed a systematic search to identify relevant studies on the evaluation of the correlation between the IL-1 gene and knee OA published up to February 2020 that met the eligibility criteria. Nine studies on a total of 2256 knees with OA and 3527 healthy knees met the eligibility criteria. Results associated with IL-1A, IL-1B, IL-1R1, and IL-1RN SNPs were extracted and compared between knees with OA and healthy knees. Methodological quality was assessed using the Newcastle–Ottawa scale (NOS). All studies with fair or good quality were included. Results The meta-analysis showed that the risk of knee OA is decreased by the IL-1RN*1 and IL-1RN*1/*1 genotypes and increased by the IL-1RN*2 and I-L1RN*1/*2 genotypes. The systematic review revealed only two studies associating the IL-1RN allele, none associating the IL-1B polymorphism, and only one study associating IL-1A and IL-1R1 polymorphisms with knee OA. Conclusions Several IL-1RN alleles and genotypes play a role in knee OA but other genetic variations in the IL-1 region were still conflicting in its association with knee OA.