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Association between an Insulin-Like Growth Factor I Gene Promoter Polymorphism and Bone Mineral Density in the Elderly: The Rotterdam Study

Department of Epidemiology and Biostatistics (F.R., J.J.H.-D., N.V., J.M.V.-D., H.A.P.P., A.G.U.) and Internal Medicine (F.R., N.V., H.A.P.P., A.G.U.), Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands; and Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana (F.R.), Bogota, Colombia

Address all correspondence and requests for reprints to: Dr. Huibert A. P. Pols, Department of Internal Medicine, Erasmus Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands. E-mail: h.pols{at}erasmusmc.nl.

Studies of the roles of variants of the IGF-I gene in the regulation of bone mineral density (BMD) have yielded conflicting results. We examined the role of a microsatellite repeat polymorphism in one of the promoter regions of the IGF-I gene in relation to femoral BMD in elderly women and men from the Rotterdam Study. We studied 5648 and 4134 individuals at baseline and follow-up (2 yr later), respectively. Femoral BMD measurements were performed using dual energy x-ray absorptiometry. In women, baseline BMD levels were, on the average, 0.02 g/cm² [95% confidence interval (CI) for difference, -0.03, -0.00 g/cm²] lower in individuals without the 192-bp allele as compared with the homozygotes for the allele (P = 0.03). The mean rate of BMD change from baseline to follow-up was -6.9 mg/cm² (95% CI, -10.8, -3.0), -4.5 mg/cm² (95% CI, -6.4, -2.5), and -2.3 mg/cm² (95% CI, -4.2, 0.3) in noncarriers, heterozygotes, and homozygotes for the 192-bp allele, respectively (P trend = 0.03). Adjustment for age and body mass index did not essentially change this relation. No such effects were observed in men. Our findings suggest that this promoter polymorphism or another functional polymorphism in linkage disequilibrium may be a genetic determinant of BMD levels and rate of bone loss in postmenopausal women.

This work was supported by The Netherlands Organization for Scientific Research (Project 014-90-001) and was part of F.R.’s M.Sc. Training Program in Genetic Epidemiology at The Netherlands Institute for Health Sciences.

Abbreviations: BMD, Bone mineral density; BMI, body mass index; CI, confidence interval; DEXA, dual energy x-ray absorptiometry.

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