Abstract
Previous studies that evaluated the association between a disintegrin and metalloprotease 12 (ADAM12) gene polymorphisms and knee osteoarthritis (KOA) have given controversial and indefinite results. Therefore, we performed a meta-analysis to confirm this correlation. We searched the PubMed, Embase, and SinoMed databases for all papers published up to April 11, 2017. Overall, five different studies, totaling 2,353 cases and 3,668 controls, were retrieved on the basis of the search criteria for KOA susceptibility related to four polymorphisms (rs3740199, rs1278279, rs1871054, and rs1044122) in the ADAM12 gene. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using Egger's and Begg's tests. The rs3740199 G/C polymorphism was found to be associated with increased KOA risk in men (e.g., CG versus GG: OR = 1.44, 95% CI = 1.02–2.04, P = 0.040), but not in the overall analysis and in analyses of other subgroups. Significantly increased associations were also found for the rs1871054 polymorphism (e.g., C versus T allele: OR = 1.85, 95% CI = 1.49–2.30, P < 0.001). However, there were no associations for the rs1278279 and rs1044122 polymorphisms. Furthermore, no obvious evidence of publication bias was detected. Our study indicated that the rs1871054 polymorphism of ADAM12 was significantly associated with increased KOA risk.
Highlights
Osteoarthritis (OA) is a common late-onset degenerative joint disease affecting millions of people worldwide
Considering the critical role of a disintegrin and metalloprotease 12 (ADAM12) in knee osteoarthritis (KOA), we performed a meta-analysis of all eligible case-control studies to obtain a more accurate picture of the association of four ADAM12 gene polymorphisms with KOA
We identified five articles (11 case-control studies, four polymorphism sites) that evaluated the association of the rs3740199, rs1278279, rs1871054, and rs1044122 polymorphisms in ADAM12 with the risk of KOA (Figure 1) [16,17,18,19,20]
Summary
Osteoarthritis (OA) is a common late-onset degenerative joint disease affecting millions of people worldwide. Considering the critical role of ADAM12 in KOA, we performed a meta-analysis of all eligible case-control studies to obtain a more accurate picture of the association of four ADAM12 gene polymorphisms (rs3740199, rs1278279, rs1871054, and rs1044122) with KOA susceptibility. For the rs3740199 polymorphism, no significant positive association was observed between KOA risk and the variant genotypes in all different genetic models in whole populations, including allelic contrast (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.93–1.12, Pheterogeneity = 0.538, P = 0.726, fixed model, Figure 2), homozygote comparison 3; dominant model: OR = 1.46, 95% CI = 1.05–2.03, Pheterogeneity = 0.420, P = 0.025, fixed model, Table 3A). For the rs1871054 polymorphism, a positive correlation was found between KOA risk in the whole analysis, including allelic contrast We analyzed the opposite effects model at the same time (Table 3B), where similar results were detected in both models, which did not influence the final conclusion
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