Preliminary results from this study were published in abstract form as Uitterlinden et al. Polymorphisms in the vitamin D receptor- and collagen type Iα1 gene predict osteoporotic fracture in women. Am J Hum Genet 1998;63(4):A223 (abstract 1279).
Interaction Between the Vitamin D Receptor Gene and Collagen Type Iα1 Gene in Susceptibility for Fracture†
Article first published online: 1 FEB 2001
Copyright © 2001 ASBMR
Journal of Bone and Mineral Research
Volume 16, Issue 2, pages 379–385, February 2001
How to Cite
Uitterlinden, A. G., Weel, A. E. A. M., Burger, H., Fang, Y., Van Duijn, C. M., Hofman, A., Van Leeuwen, J. P. T. M. and Pols, H. A. P. (2001), Interaction Between the Vitamin D Receptor Gene and Collagen Type Iα1 Gene in Susceptibility for Fracture. J Bone Miner Res, 16: 379–385. doi: 10.1359/jbmr.2001.16.2.379
- Issue published online: 2 DEC 2009
- Article first published online: 1 FEB 2001
- Manuscript Accepted: 11 SEP 2000
- Manuscript Revised: 11 AUG 2000
- Manuscript Received: 25 JAN 1999
- complex trait
Osteoporosis is a common disease with a strong genetic component. Polymorphisms in the vitamin D receptor (VDR) gene have been implicated in osteoporosis but explain only a small part of the genetic effect on bone mineral density (BMD) while their effect on fractures is still uncertain. Recently, a G to T polymorphism in an Sp1 site in the collagen type Iα1 (COLIA1) gene was found to be associated with reduced BMD and with increased fracture risk. To analyze the combined influence of polymorphisms in the VDR gene and the COLIA1 gene in determining the susceptibility to osteoporotic fracture, we studied 1004 postmenopausal women. The “baT ” VDR haplotype, constructed from three adjacent restriction fragment length polymorphisms, was found to be overrepresented among fracture cases (p = 0.009). This corresponded to an odds ratio (OR) of 1.8 (95% CI, 1.0–3.3) for heterozygous carriers and 2.6 (95%CI, 1.4–5.0) for homozygous carriers of the risk haplotype. The effect was similar for vertebral and nonvertebral fractures and, most importantly, independent of BMD. We observed significant interaction (p = 0.03) between VDR and COLIA1 genotype effects. Fracture risk was not VDR genotype-dependent in the COLIA1 “reference” group (genotype GG) while in the COLIA1 “risk” group (genotypes GT and TT) the risk of fracture was 2.1 (95%CI, 1.0–4.4) for heterozygous and 4.4 (95%CI, 2.0–9.4) for homozygous carriers of the VDR risk haplotype. We conclude that both the VDR and the COLIA1 polymorphisms are genetic markers for osteoporotic fracture in women, independent of BMD. Our data indicate that interlocus interaction is likely to be an important component of osteoporotic fracture risk.