The Association between Common Vitamin D Receptor Gene Variations and Osteoporosis: A Participant-Level Meta-Analysis
Year: 2006
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures. DESIGN: Prospective multicenter large-scale association study. SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. PARTICIPANTS: 26,242 participants (18,405 women). MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.
Source: Annals of Internal Medicine
Authors: André G. Uitterlinden, Stuart H. Ralston, Maria Luisa Brandi, Alisoun H. Carey, Daniel Grinberg, Bente L. Langdahl, Paul Lips, Roman Lorenc, Barbara Obermayer-Pietsch, Jonathan Reeve, David M. Reid, Antonietta Amedei, Amelia Bassiti, Mariona Bustamante, Lise Bjerre Husted, Adolfo Diez-Perez, Harald Dobnig, Alison M. Dunning, Anna Enjuanes, Astrid Fahrleitner-Pammer, Yue Fang, Elzbieta Karczmarewicz, Marcin Kruk, Johannes P.T.M. van Leeuwen, Carmelo Mavilia, Joyce B.J. van Meurs, Jon Mangion, Fiona E.A. McGuigan, Huibert A.P. Pols, Wilfried Renner, Fernando Rivadeneira, Natasja M. van Schoor, Serena Scollen, Rachael E. Sherlock, John P.A. Ioannidis, and APOSS Investigators, and EPOS Investigators, and EPOLOS Investigators, and FAMOS Investigators, and LASA Investigators, and Rotterdam Study Investigators, for the GENOMOS Study*
Institutions: Universitat Autònoma de Barcelona, University of Ioannina, University of Aberdeen, University of Cambridge, Western General Hospital, Erasmus MC, Aarhus University Hospital, Hospital Del Mar, University of Florence, Universitat de Barcelona, Foundation for Research and Technology Hellas, Amsterdam UMC Location Vrije Universiteit Amsterdam, University of Edinburgh, Oxagen (United Kingdom), Aarhus University, Vrije Universiteit Amsterdam, Children's Memorial Health Institute, Medical University of Graz, Erasmus University Rotterdam
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2147162951