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.

The role of genetic polymorphisms of interleukin-1 (IL-1R1 and IL-1RN) in primary knee osteoarthritis in Indonesia

“…However, our study showed no association between IL-1RN gene variants rs419598, rs9005, and rs315943 and IL-1R1 rs2287047. Conflicting results were also found in previous systematic reviews and meta-analyses regarding the effect of genetic polymorphisms on the incidence of primary knee OA and clinical, radiologic, and laboratory findings 19 . Studies on the relationship of polymorphisms of the IL-1 family with the severity of knee OA are still scarce.…”

Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

“…In addition, another important aspect of OA is the synovial change ( 21 ). IL-1RN is one of the cytokines implicated in OA at the inflammation level ( 22 ). It has been reported that the IL-1–IL-17 signaling axis induces cartilage destruction and OA development by enhancing the expression of catabolic factors ( 23 ).…”

Why Does Rehabilitation Not (Always) Work in Osteoarthritis? Does Rehabilitation Need Molecular Biology?

“…This fact was used to create artificial antagonist receptor-like Anakinra (approved by FDA for clinical use) to reduce excessive IL-1 activity [73]. Budhiparama et al in a meta-analysis concluded that IL-1 single nucleotide gene polymorphism determines different knee arthrosis probability [74]. The effect of IL-1 single nucleotide polymorphism was described in 2004, leading to the conclusion that the real effect of resistant exercise depends on Il-1 polymorphism [75].…”