DIFFERENTIAL ALLELIC EXPRESSION OF THE TYPE-II COLLAGEN GENE (COL2A1)IN OSTEOARTHRITIC CARTILAGE

Osteoarthritis (OA) is a common debilitating disease resulting from th e degeneration of articular cartilage. The major protein of cartilage is type II collagen, which is encoded by the COL2A1 gene. Mutations at this locus have been discovered in several individuals with inherited disorders of cartilage. We have identified 27 primary OA patients who are heterozygous for sequence dimorphisms located in the coding regio n of COL2A1. These dimorphisms were used to distinguish the mRNA outpu t from each of the two COL2A1 alleles in articular cartilage obtained from each patient. Three patients demonstrated differential allelic ex pression and produced <12% of the normal level of mRNA from one of the ir COL2A1 alleles. The same allele shows reduced expression in ah thre e patients, and this allele is more frequent in a well-defined OA popu lation than in a control group, suggesting the possible existence of a rare COL2A1 allele that predisposes to OA.