CONCISE REPORTS A genetic association study of the IGF-1 gene and radiological osteoarthritis in a population-based cohort study (the Rotterdam study)

Objective—A genetic association study was performed to investigate whether radiographical osteoarthritis (ROA) was associated with specific genotypes of the insulin-like growth factor I (IGF-1) gene. Methods—Subjects aged 55–65 years were selected from a population-based study of which ROA at the knee, hip, spine, and hand was assessed. Genotypes were determined of a polymorphism in the promoter region of the IGF-1 gene. Results—The IGF-1 locus was significantly associated with the presence of ROA (overall adjusted OR for heterozygous subjects = 1.9, 95% CI 1.2, 3.1 and for homozygous subjects 3.6, 95% CI 0.8, 16.2). Conclusion—These results suggest that variation at the IGF-1 locus is associated with ROA development and may play a part in ROA pathogenesis. To confirm these findings replication in another population-based sample is needed. (Ann Rheum Dis 1998;57:371–374) Osteoarthritis (OA) is a disease characterised by the degradation of articular cartilage and formation of new bone (osteophytes and sclerosis). Several reports suggest that genetic influences contribute considerably to the development of OA. 2 The relevance of the genetic component, however, varies among subgroups of patients and as yet it is not clear which genes are involved. Insulin-like growth factor 1 (IGF-1) stimulates chondrocytes to synthesise extracellular matrix (ECM) components in cartilage. 5 Its action is mediated through the type 1 IGF receptor. The function of IGF-1 and its receptor in cartilage formation both during developmental stages and remodelling of adult cartilage may be relevant to the aetiology of OA. IGF-1 may also influence OA by osteophyte formation. Although osteophyte growth during OA progression and bone mineral density (BMD) is positively correlated to high serum IGF-1 concentrations, 7 no consistent relation between serum IGF-1 concentrations and OA has been found. 9 Furthermore, serum IGF-1 is inversely correlated to age and body mass index (BMI). As individual IGF-1 concentrations are liable to temporal variations, assessing the role of IGF-1 in OA by serum concentrations is complex. We have examined the relation between the IGF-1 gene and the presence of radiographical OA (ROA) in subjects aged 55–65 years.