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

Purpose Interleukin-1 is the main proinflammatory cytokine in osteoarthritis (OA). Several single-nucleotide polymorphisms (SNPs) within the IL-1 gene cluster (IL-1 beta, 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.

Automated summary

This study conducted a meta-analysis and systematic review to investigate the associations between IL-1 single-nucleotide polymorphisms (SNPs) and knee osteoarthritis (OA). The results showed that certain alleles and genotypes in the IL-1 gene cluster, particularly IL-1RN, are associated with the risk of knee OA. However, the associations of other genetic variations in the IL-1 region with knee OA remain conflicting.