title: Association of matrilin-3 polymorphisms with spinal disc degeneration and osteoarthritis of the first carpometacarpal joint of the hand.
abstract: BACKGROUND
  Seven polymorphisms in the matrilin-3(MATN3) gene were previously tested for genetic association with hand osteoarthritis in an Icelandic cohort. One of the variants, involving a conserved amino acid substitution (T303M; SNP5), was related to idiopathic hand osteoarthritis.
  
  
  OBJECTIVE
  To investigate SNP5 and two other promising polymorphisms (rs2242190; SNP3, rs8176070; SNP6) for association with radiographic and symptomatic hand osteoarthritis phenotypes, as well as other heritable phenotypes.
  
  
  METHODS
  Polymorphisms were examined in two distinct cohorts of subjects: a population based sample from the Rotterdam study (n = 809), and affected siblings from the genetics, osteoarthrosis and progression (GARP) study (n = 382).
  
  
  RESULTS
  The originally described association of T303M with the hand osteoarthritis phenotype was not observed in the populations studied. In the Rotterdam sample, however, carrying the T allele of T303M conferred an odds ratio of 2.9 (95% confidence interval (CI), 1.2 to 7.3; p = 0.02) for spinal disc degeneration. In the GARP study, carriers of the A allele of SNP6 had an odds ratio of 2.0 (95% CI, 1.3 to 3.1, p = 0.004) for osteoarthritis of the first carpometacarpal joint (CMC1) as compared with the Rotterdam sample as a control group. Subsequent haplotype analysis showed that a common haplotype, containing the risk allele of SNP6, conferred a significant risk in sibling pairs with CMC1 osteoarthritis (odds ratio = 1.7 (95% CI, 1.1 to 2.7, p = 0.02)).
  
  
  CONCLUSIONS
  These associations suggest that the MATN3 region also determines susceptibility to spinal disc degeneration and CMC1 osteoarthritis.
authors.affiliation: Section of Molecular Epidemiology, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL Leiden, Netherlands. j.min@lumc.nl
authors.forename: J L
authors.initials: JL
authors.lastname: Min
authors.forename: I
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: N
authors.initials: N
authors.lastname: Riyazi
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: J J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: A B
authors.initials: AB
authors.lastname: Seymour
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
mesh_terms: D000483:Alleles; D018450:Disease Progression; D004812:Epidemiologic Methods; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D050823:Hand Joints / Q000473:pathology; D006239:Haplotypes; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D009426:Netherlands; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D025241:Spondylarthritis / Q000235:genetics* / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins; D064235:Matrilin Proteins