Association study of MMP8 gene in osteoarthritis

ABSTRACT

Objectives: Osteoarthritis (OA) is a joint disease common in the elderly. There is a prior functional evidence for different matrix metalloproteinases (MMPs), such as MMP8 and MMP9, having a role in the breakdown of cartilage extracellular matrix in OA. Thus, we analyzed whether the common genetic variants of MMP8 and MMP9 contribute to the risk of OA. Materials and methods: In total, 13 common tagging single-nucleotide polymorphisms (SNPs) were studied in a discovery knee OA cohort of 185 cases and 895 controls. For validation, two knee OA replication cohorts and two hand OA replication cohorts were studied (altogether 1369 OA cases, 4445 controls in the five cohorts). The χ² test for individual study cohorts and Cochran–Mantel–Haenszel test for combined meta-analysis were calculated using Plink. Results: The rs1940475 SNP in MMP8 showed suggestive association in the discovery cohort (OR = 0.721, 95% CI 0.575–0.906; p = 0.005). Other knee and hand OA replication study cohorts showed similar trend for the predisposing allele without reaching statistical significance in independent replication cohorts nor in their meta-analysis (p > 0.05). Meta-analysis of all five hand and knee OA study cohorts yielded a p-value of 0.027 (OR = 0.904, 95% CI 0.826–0.989). Conclusions: Initial analysis of the MMP8 gene showed suggestive association between rs1940475 and knee OA, but the finding did not replicate in other study cohorts, even though the trend for predisposing allele was similar in all five cohorts. MMP-8 is a good biological candidate for OA, but our study did not find common variants with significant association in the gene.

KEYWORDS:

• Association
• gene
• matrix metalloproteinase 8
• osteoarthritis

Acknowledgments

We would like to warmly thank the study subjects for their participation in the present study. Minna Suvela is thanked for her technical expertise in the genotyping process. Michele C. Battié, Heidi Lönnberg, and Aki Salo are thanked for their contribution.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

The financial supporters of the study are thanked for making the present study possible to conduct: TBDP National Doctoral Programme of Musculoskeletal Disorders and Biomaterials (formerly known as TBGS National Graduate School of Musculoskeletal Disorders and Biomaterials, and TULES Graduate School), Finnish Cultural Foundation, University of Helsinki foundation, Biomedicum Helsinki foundation, Otto A. Malm foundation, Emil Aaltonen Foundation. The Spanish study was supported by the Xunta de Galicia and by the Fondo de Investigacion Sanitaria of the Instituto de Salud Carlos III (Spain) grant 09/01431, which was partially funded by the European Union Fondo Europeo de Desarrollo Regional Program. The Finnish Twin Cohort has been supported by the Academy of Finland Centre of Excellence in Complex Disease Genetics (grants 213506 and 129680).