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Sibling Pair Linkage and Association Studies between Bone Mineral Density and the Insulin-Like Growth Factor I Gene Locus¹

Departments of Medicine (I.T., M.P., S.L.H., C.C.J., M.J.E.) and Medical and Molecular Genetics (D.L.K., J.C.C., P.M.C., M.J.E.), Indiana University School of Medicine, Indianapolis, Indiana 46202

Address all correspondence and requests for reprints to: Michael J. Econs, M.D., F.A.C.P., F.A.C.E., Indiana University School of Medicine, 975 West Walnut Street, IB 445, Indianapolis, Indiana 46202. E-mail: mecons{at}iupui.edu

A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Insulin-like growth factor I (IGF-I) is an attractive candidate gene for osteoporosis susceptibility, because IGF-I has marked effects on bone cells and has been implicated in the pathogenesis of osteoporosis. The IGF-I gene contains a microsatellite repeat polymorphism approximately 1 kb upstream from the IGF-I gene transcription start site, and previous investigators have found a higher prevalence of the 192/192 genotype of this polymorphism among men with idiopathic osteoporosis compared to controls. In this study we used this IGF-I polymorphism to test for an association between this polymorphism and BMD in our large population of premenopausal women (1 sister randomly chosen from 292 Caucasian and 71 African-American families). We also used this polymorphism to detect linkage to BMD elsewhere in the IGF-I gene or in a nearby gene using sibling pair linkage analysis in healthy premenopausal sister pairs (542 sibling pairs: 418 Caucasian and 124 African-American). Neither test provided any evidence of linkage or association between the IGF-I gene locus and spine or femoral neck BMD in Caucasians or African-Americans.

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