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Association of matrilin-3 polymorphisms with spinal disc degeneration and osteoarthritis of the first carpometacarpal joint of the hand

J L Min¹, I Meulenbelt¹, N Riyazi², M Kloppenburg², J J Houwing-Duistermaat³, A B Seymour⁴, C M van Duijn⁵, P E Slagboom¹

¹ Molecular Epidemiology, Leiden University Medical Centre (LUMC), Leiden, Netherlands
² Rheumatology, LUMC, Leiden
³ Medical Statistics, LUMC, Leiden
⁴ Discovery Pharmacogenomics, Pfizer Global Research & Development, Groton, USA
⁵ Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, Netherlands

Correspondence to:
Josine Min
Leiden University Medical Centre, Section of Molecular Epidemiology, Wassenaarseweg 72, 2333 AL Leiden, Netherlands; j.min{at}lumc.nl

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.

Abbreviations: ACR, American College of Rheumatology; CMC1, first carpometacarpal joint; DIP, distal interphalangeal joint; GARP, Genetics, Osteoarthrosis and Progression study; htSNP, haplotype tag SNP; HWE, Hardy–Weinberg equilibrium; ROA, radiographic osteoarthritis; SNP, single nucleotide polymorphism

Keywords: osteoarthritis; matrilin-3

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