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Previous Volume 338:1016-1021 April 9, 1998 Number 15 Next

Relation of Alleles of the Collagen Type I1 Gene to Bone Density and the Risk of Osteoporotic Fractures in Postmenopausal Women

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ABSTRACT

Background Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type I1, a bone-matrix protein.

Methods We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction–based assay. We then related the genotypes to bone mineral density and the occurrence of osteoporotic fractures in these women.

Results As compared with the 1194 women with the SS genotype, the 526 women with the Ss genotype had 2 percent lower bone mineral density at the femoral neck (P = 0.003) and the lumbar spine (P = 0.02); the 58 women with the ss genotype had reductions of 4 percent at the femoral neck (P = 0.05) and 6 percent at the lumbar spine (P = 0.005). These differences increased with age (P = 0.01 for modification by age of the effect of COLIA1 on femoral-neck bone density, and P = 0.004 for modification of the effect on lumbar-spine bone density). Women with the Ss and ss genotypes were overrepresented among the 111 women who had incident nonvertebral fractures (relative risk per copy of the s allele, 1.5; 95 percent confidence interval, 1.1 to 2.1).

Conclusions The COLIA1 polymorphism is associated with reduced bone density and predisposes women to osteoporotic fractures.

Source Information

From the Departments of Internal Medicine III (A.G.U., J.P. T.M.L., H.A.P.P.) and Epidemiology and Biostatistics (A.G.U., H.B., Q.H., F.Y., A.H., H.A.P.P.), Erasmus University Medical School, Rotterdam, the Netherlands; and the Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom (F.E.A.M., S.F.A.G., S.H.R.).

Address reprint requests to Dr. Uitterlinden at the Department of Internal Medicine III, FGG-EUR, Erasmus University Medical School, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands.

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