Association of matrilin-3 polymorphisms with spinal disc degeneration and with osteoarthritis of the CMC 1 joint of the hand

Seven polymorphisms in the matrilin-3 (MATN3) gene were previously tested for genetic association with hand osteoarthritis (OA) in an Icelandic cohort. One of the variants, involving a conserved amino acid substitution (T303M; SNP5), was related to idiopathic hand OA. T303M and two other promising polymorphisms (rs2242190; SNP3, rs8176070; SNP6) were investigated for association with radiographic and symptomatic hand OA phenotypes, as well as other heritable phenotypes. Polymorphisms were examined in two distinct cohorts of subjects: a populationbased sample of the Rotterdam study (n = 809) and affected siblings from the Genetics, osteoARthritis and Progression (GARP) study (n = 382). The originally described association of T303M with the hand OA 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), 1.2-7.3, 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, 1.3-3.1, P = 0.004) for OA 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 OA of 1.7 (95 % CI, 1.1-2.7, P = 0.02). These associations suggest that the MATN3 region also determines susceptibility to spinal disc degeneration and CMC1 OA. CHAPTER