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Interaction between the vitamin D receptor gene and collagen type Ialpha1 gene in susceptibility for fracture.
J Bone Miner Res. 2001 Feb; 16(2):379-85.JB

Abstract

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 Ialpha1 (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.

Authors+Show Affiliations

Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11204438

Citation

Uitterlinden, A G., et al. "Interaction Between the Vitamin D Receptor Gene and Collagen Type Ialpha1 Gene in Susceptibility for Fracture." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 16, no. 2, 2001, pp. 379-85.
Uitterlinden AG, Weel AE, Burger H, et al. Interaction between the vitamin D receptor gene and collagen type Ialpha1 gene in susceptibility for fracture. J Bone Miner Res. 2001;16(2):379-85.
Uitterlinden, A. G., Weel, A. E., Burger, H., Fang, Y., van Duijn, C. M., Hofman, A., van Leeuwen, J. P., & Pols, H. A. (2001). Interaction between the vitamin D receptor gene and collagen type Ialpha1 gene in susceptibility for fracture. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 16(2), 379-85.
Uitterlinden AG, et al. Interaction Between the Vitamin D Receptor Gene and Collagen Type Ialpha1 Gene in Susceptibility for Fracture. J Bone Miner Res. 2001;16(2):379-85. PubMed PMID: 11204438.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction between the vitamin D receptor gene and collagen type Ialpha1 gene in susceptibility for fracture. AU - Uitterlinden,A G, AU - Weel,A E, AU - Burger,H, AU - Fang,Y, AU - van Duijn,C M, AU - Hofman,A, AU - van Leeuwen,J P, AU - Pols,H A, PY - 2001/2/24/pubmed PY - 2001/4/21/medline PY - 2001/2/24/entrez SP - 379 EP - 85 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 16 IS - 2 N2 - 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 Ialpha1 (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. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/11204438/Interaction_between_the_vitamin_D_receptor_gene_and_collagen_type_Ialpha1_gene_in_susceptibility_for_fracture_ L2 - https://doi.org/10.1359/jbmr.2001.16.2.379 DB - PRIME DP - Unbound Medicine ER -