The role of genetic variants of A disintegrin and metalloproteinase domain 12 in osteoarthritis: A synthesis of meta-analysis reviews

Abstract

Genes play an important role in the aetiology of osteoarthritis (OA) and A Disintegrin, and Metalloproteinase Domain 12 (ADAM12) gene single nucleotide polymorphisms (SNPs) may be involved. Previous review studies have investigated the association of four ADAM12 gene SNPs, with OA, but it is unclear whether the evidence from these reviews is consistent. The purpose of this umbrella systematic review was to examine existing meta-analysis evidence with the primary objective of comparing and contrasting the findings on the association of ADAM12 SNPs (rs3740199, rs1871054, rs1278279 and rs1044122) with OA, in order to obtain a more accurate picture on the role of ADAM12 in OA. We performed a comprehensive search on PubMed, Google Scholar, Web of Science, Cochrane and Medline to identify meta-analyses of studies that examined associations between ADAM12 SNPs with OA up to 2021. Eight meta-analyses with 67750 participants, 30983 cases and 36767 controls were included in this umbrella systematic review. Four meta-analyses showed that rs3740199 was significantly associated with increased risk for knee osteoarthritis (KOA) in men. One meta-analysis indicated that the rs1044122 was significantly associated with increased risk for KOA in men. Six meta-analyses concluded that rs1871054 increased the risk of OA susceptibility in Asians. However, no association was found between rs1278279 and OA. Overall, studies have yielded inconsistent results. Some indicated association of a particular SNP with OA, while others reported conflicting findings. The discrepant results across studies may be due to factors such as diversity in the genetic make-up of study samples, race and country of the study population.