title: The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis.
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.
  
  
  METHODS
  Prospective multicenter large-scale association study.
  
  
  METHODS
  The Genetic Markers for Osteoporosis consortium, involving 9 European research teams.
  
  
  METHODS
  26,242 participants (18,405 women).
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Erasmus MC, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.forename: Alisoun H
authors.initials: AH
authors.lastname: Carey
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.forename: Roman
authors.initials: R
authors.lastname: Lorenc
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
authors.forename: Jonathan
authors.initials: J
authors.lastname: Reeve
authors.forename: David M
authors.initials: DM
authors.lastname: Reid
authors.forename: Antonietta
authors.initials: A
authors.lastname: Amedei
authors.forename: Antonietta
authors.initials: A
authors.lastname: Amidei
authors.forename: Amelia
authors.initials: A
authors.lastname: Bassiti
authors.forename: Mariona
authors.initials: M
authors.lastname: Bustamante
authors.forename: Lise Bjerre
authors.initials: LB
authors.lastname: Husted
authors.forename: Adolfo
authors.initials: A
authors.lastname: Diez-Perez
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Anna
authors.initials: A
authors.lastname: Enjuanes
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.forename: Yue
authors.initials: Y
authors.lastname: Fang
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Karczmarewicz
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruk
authors.forename: Johannes P T M
authors.initials: JP
authors.lastname: van Leeuwen
authors.forename: Carmelo
authors.initials: C
authors.lastname: Mavilia
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Jon
authors.initials: J
authors.lastname: Mangion
authors.forename: Fiona E A
authors.initials: FE
authors.lastname: McGuigan
authors.forename: Huibert A P
authors.initials: HA
authors.lastname: Pols
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.forename: Serena
authors.initials: S
authors.lastname: Scollen
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Sherlock
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D000328:Adult; D000368:Aged; D015519:Bone Density / Q000235:genetics*; D000071616:CDX2 Transcription Factor; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D050723:Fractures, Bone / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; C053864:endodeoxyribonuclease BsmI; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific; C038485:GGGCCC-specific type II deoxyribonucleases; C027046:TCGA-specific type II deoxyribonucleases