Identification of sequence polymorphisms of the COMP (cartilage oligomericmatrix protein) gene and association study in osteoarthrosis of the knee and hip joints

Osteoarthrosis (OA) is a common cause of musculoskeletal disability charact erized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to b e determined. Hereditary osteochondral dysplasias produce severe, early-ons et OA and hence are models for common idiopathic OA. Among them are pseudoa chondroplasia and multiple epiphyseal dysplasia, both of which are caused b y mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefo re, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gone with their flanking int ron sequences and the promoter region. We identified 16 polymorphisms, of w hich 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the kne e and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was n o significant difference in haplotypes. These results do not support an ass ociation between COMP and OA in the Japanese population.