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.

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.

• Authors: J L Min, I Meulenbelt, N Riyazi, M Kloppenburg, J J Houwing-Duistermaat, A B Seymour, C M van Duijn, P E Slagboom
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 65 Issue 8 Pg. 1060-6 (Aug 2006) ISSN: 0003-4967 [Print] England
• PMID: 16396979 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• Matrilin Proteins

Topics

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