TYPE II COLLAGEN GENE MUTATIONS IN OSTEOARTHRITIS

骨关节炎中的 II 型胶原蛋白基因突变

• 批准号: 2081206
• 负责人: ROLAND W MOSKOWITZ
• 金额: $ 17.57万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-15 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2081206
• 关键词: biomarker; body fluids; cartilage metabolism; collagen; disease /disorder classification; family genetics; gene mutation; human genetic material tag; human population genetics; human tissue; nucleic acid probes; osteoarthritis; pathology; phenotype; polymerase chain reaction; proteoglycan

The etiology of osteoarthritis (OA), is at present unknown. Genetic, environmental, metabolic and biomechanical factors have been suggested as playing possible roles.Interest in a genetic role for the etiology of OA has expanded based on clinical identification of positive inheritance patterns in certain disease sub-sets such as Heberden's nodes, differences in the prevalence of OA among different races and populations, increased frequency of OA in patients with HLA-A1B8 and HLA- B8 and the recent demonstration of a type-II collagen gene (COL2A1) mutation as a cause of primary generalized OA in at least one form of the disease, primary OA associated with a spinal chondrodysplasia. The mutation resulted in the replacement of arginine at position 519 of the a1(II) collagen molecule to cysteine, an amino acid not found in type-II collagen from humans or other species studied so far. Further studies in our laboratory have demonstrated the a1-519 mutation in an additional two of seven families studied. The studies proposed in this proposal will: (1) determine the prevalence of the a-519 mutation with strong family clustering of generalized OA and in non-related individuals with hip/knee OA; and identify other mutations in the COL2A1 gene; and (2) study body fluid biochemical markers of cartilage (collagen, proteoglycan) metabolism to assess OA etiopathologic mechanisms and clinical utility. The results of these studies will allow us to develop DNA probes; to delineate disease susceptibility of individuals to OA; and to correlate various gene defects with varying phenotypic patterns of disease severity. Assessment of biochemical markers of cartilage will add to our understanding of OA disease mechanisms.

骨关节炎（OA）的病因目前尚不清楚。遗传的,