title: Missense single nucleotide polymorphism of the ADAM12 gene is associated with radiographic knee osteoarthritis in middle-aged Estonian cohort.
abstract: OBJECTIVE
  One of the recognized candidate genes of osteoarthritis (OA) is the ADAM metallopeptidase domain 12 (meltrin alpha) gene. We investigated the potential role of two single nucleotide polymorphisms (SNP) of the ADAM12 gene in susceptibility to radiographic knee OA and its progression in an Estonian cohort.
  
  
  METHODS
  The rs3740199 and rs1871054 polymorphisms were genotyped according to restriction fragment polymorphism in a population-based cohort consisting of 189 subjects selected from the age group 32-55 years. The radiological features of OA were measured in the tibio- and patellofemoral joints (PFJ). The X-ray investigation was repeated 3 years later for estimation of OA progression.
  
  
  RESULTS
  We found statistically significant association between rs3740199 polymorphism and patellofemoral OA in male patients (P=0.014), genetic risk was mostly related to CC homozygosity. The same SNP also affected the presence of advanced grade (II+III) osteophytes in the whole group (P=0.042) and the occurrence of osteophytes on the patellar margins in the PFJ (P=0.046). In OA progression the most significant association was found between joint space narrowing of the tibiofemoral joint and rs3740199 SNP in women (P=0.018). The rs1871054 polymorphism was not related to OA susceptibility or to progression traits. In our study the haplotype GC (rs3740199/rs1871054) was associated with reduced risk for development of osteophytes in the PFJ (P=0.041).
  
  
  CONCLUSIONS
  We conclude that rs3740199 polymorphism may affect occurrence of knee OA and its progression. We also hypothesize that the genetic contribution of ADAM12 to OA is remarkably gender-dependent and anatomical site-specific.
authors.affiliation: Department of Laboratory Medicine, University of Tartu, Puusepa 6-222, Tartru 51014, Estonia. irina.kerna@kliinikum.ee
authors.forename: I
authors.initials: I
authors.lastname: Kerna
authors.forename: K
authors.initials: K
authors.lastname: Kisand
authors.forename: A E
authors.initials: AE
authors.lastname: Tamm
authors.forename: M
authors.initials: M
authors.lastname: Lintrop
authors.forename: K
authors.initials: K
authors.lastname: Veske
authors.forename: A O
authors.initials: AO
authors.lastname: Tamm
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072199:ADAM12 Protein; D000328:Adult; D018450:Disease Progression; D004957:Estonia; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011859:Radiography
chemical_list: D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human