Advanced

The association between common vitamin D receptor gene variations and osteoporosis : a participant-level meta-analysis

Uitterlinden, André G ; Ralston, Stuart H ; Brandi, Maria Luisa ; Carey, Alisoun H ; Grinberg, Daniel ; Langdahl, Bente L ; Lips, Paul ; Lorenc, Roman ; Obermayer-Pietsch, Barbara and Reeve, Jonathan , et al. (2006) In Annals of Internal Medicine 145(4). p.255-264
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adult, Aged, Bone Density, CDX2 Transcription Factor, Deoxyribonucleases, Type II Site-Specific, Female, Fractures, Bone, Genotype, Haplotypes, Homeodomain Proteins, Humans, Male, Middle Aged, Osteoporosis, Polymorphism, Genetic, Promoter Regions, Genetic, Prospective Studies, Receptors, Calcitriol, Journal Article, Meta-Analysis, Multicenter Study, Research Support, Non-U.S. Gov't
in
Annals of Internal Medicine
volume
145
issue
4
pages
10 pages
publisher
American College of Physicians
external identifiers
  • pmid:16908916
  • scopus:33747115419
  • pmid:16908916
ISSN
0003-4819
language
English
LU publication?
yes
id
3f6e5720-0856-442e-bfe3-3be1fa66c149 (old id 1136320)
alternative location
http://www.annals.org/cgi/content/abstract/145/4/255
date added to LUP
2016-04-01 12:30:23
date last changed
2019-12-04 02:37:22
@article{3f6e5720-0856-442e-bfe3-3be1fa66c149,
  abstract     = {<p>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.</p><p>OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures.</p><p>DESIGN: Prospective multicenter large-scale association study.</p><p>SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams.</p><p>PARTICIPANTS: 26,242 participants (18,405 women).</p><p>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.</p><p>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).</p><p>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.</p><p>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.</p>},
  author       = {Uitterlinden, André G and Ralston, Stuart H and Brandi, Maria Luisa and Carey, Alisoun H and Grinberg, Daniel and Langdahl, Bente L and Lips, Paul and Lorenc, Roman and Obermayer-Pietsch, Barbara and Reeve, Jonathan and Reid, David M and Amedei, Antonietta and Amidei, Antonietta and Bassiti, Amelia and Bustamante, Mariona and Husted, Lise Bjerre and Diez-Perez, Adolfo and Dobnig, Harald and Dunning, Alison M and Enjuanes, Anna and Fahrleitner-Pammer, Astrid and Fang, Yue and Karczmarewicz, Elzbieta and Kruk, Marcin and van Leeuwen, Johannes P T M and Mavilia, Carmelo and van Meurs, Joyce B J and Mangion, Jon and McGuigan, Fiona E A and Pols, Huibert A P and Renner, Wilfried and Rivadeneira, Fernando and van Schoor, Natasja M and Scollen, Serena and Sherlock, Rachael E and Ioannidis, John P A},
  issn         = {0003-4819},
  language     = {eng},
  month        = {08},
  number       = {4},
  pages        = {255--264},
  publisher    = {American College of Physicians},
  series       = {Annals of Internal Medicine},
  title        = {The association between common vitamin D receptor gene variations and osteoporosis : a participant-level meta-analysis},
  url          = {http://www.annals.org/cgi/content/abstract/145/4/255},
  volume       = {145},
  year         = {2006},
}