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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. OBJECTIVES: 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.

Original publication

DOI

10.1136/ard.2005.045153

Type

Journal article

Journal

Ann Rheum Dis

Publication Date

08/2006

Volume

65

Pages

1060 - 1066

Keywords

Alleles, Disease Progression, Epidemiologic Methods, Extracellular Matrix Proteins, Female, Genetic Predisposition to Disease, Hand Joints, Haplotypes, Humans, Male, Matrilin Proteins, Middle Aged, Netherlands, Osteoarthritis, Polymorphism, Genetic, Prospective Studies, Spondylarthritis