title: Association study of MMP8 gene in osteoarthritis.
abstract: OBJECTIVE
  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.
  
  
  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 χ(2) 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.
authors.affiliation: a Institute for Molecular Medicine Finland FIMM, University of Helsinki , Helsinki , Finland.|b Department of Public Health , University of Helsinki , Helsinki , Finland.|c Department of Medical Genetics , University of Helsinki , Helsinki , Finland.|d Public Health Genomics Unit, National Institute for Health and Welfare , Helsinki , Finland.
authors.forename: Annu
authors.initials: A
authors.lastname: Näkki
authors.affiliation: e Laboratorio Investigacion 10 , Instituto de Investigacion Sanitaria- Hospital Clinico Universitario de Santiago , Santiago de Compostela , Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodriguez-Fontenla
authors.affiliation: e Laboratorio Investigacion 10 , Instituto de Investigacion Sanitaria- Hospital Clinico Universitario de Santiago , Santiago de Compostela , Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: f ORTON Orthopedic Hospital , Invalid Foundation , Helsinki , Finland.
authors.forename: Arsi
authors.initials: A
authors.lastname: Harilainen
authors.affiliation: g Department of Epidemiology and Biostatistics , Finnish Institute of Occupational Health , Helsinki , Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Leino-Arjas
authors.affiliation: h National Institute for Health and Welfare , Helsinki , Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Heliövaara
authors.affiliation: h National Institute for Health and Welfare , Helsinki , Finland.|i Department of Chronic Disease Prevention , The National Institute for Health and Welfare , Helsinki , Finland.|j Department of General Practice and Primary Health Care , University of Helsinki , Helsinki , Finland.|k Unit of General Practice , Helsinki University Central Hospital , Helsinki , Finland.|l Folkhälsan Research Center , Helsinki , Finland.|m Vasa Central Hospital , Vasa , Finland.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.affiliation: f ORTON Orthopedic Hospital , Invalid Foundation , Helsinki , Finland.
authors.forename: Kaj
authors.initials: K
authors.lastname: Tallroth
authors.affiliation: n Faculty of Rehabilitation Medicine , University of Alberta , Edmonton , Canada.
authors.forename: Tapio
authors.initials: T
authors.lastname: Videman
authors.affiliation: a Institute for Molecular Medicine Finland FIMM, University of Helsinki , Helsinki , Finland.|b Department of Public Health , University of Helsinki , Helsinki , Finland.|o Department of Mental Health , National Institute for Health and Welfare , Helsinki , Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: a Institute for Molecular Medicine Finland FIMM, University of Helsinki , Helsinki , Finland.
authors.forename: Janna
authors.initials: J
authors.lastname: Saarela
authors.affiliation: p Department of Health Sciences , University of Jyväskylä, Jyväskylä , Finland.
authors.forename: Urho M
authors.initials: UM
authors.lastname: Kujala
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D020641:Polymorphism, Single Nucleotide
chemical_list: C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8
keywords: Association; gene; matrix metalloproteinase 8; osteoarthritis