TY - JOUR
T1 - The association between common vitamin D receptor gene variations and osteoporosis
T2 - A participant-level meta-analysis
AU - APOSS investigators
AU - EPOS investigators
AU - EPOLOS investigators
AU - FAMOS investigators
AU - LASA investigators
AU - Rotterdam Study investigators
AU - Uitterlinden, André
AU - Ralston, Stuart H.
AU - Brandi, Maria Luisa
AU - Carey, Alisoun H.
AU - Grinberg, Daniel
AU - Langdahl, Bente L.
AU - Lips, Paul
AU - Lorenc, Roman
AU - Obermayer-Pietsch, Barbara
AU - Reeve, Jonathan
AU - Reid, David M.
AU - Amedei, Antonietta
AU - Bassiti, Amelia
AU - Bustamante, Mariona
AU - Husted, Lise Bjerre
AU - Diez-Perez, Adolfo
AU - Dobnig, Harald
AU - Dunning, Alison M.
AU - Enjuanes, Anna
AU - Fahrleitner-Pammer, Astrid
AU - Fang, Y (Yue)
AU - Karczmarewicz, Elzbieta
AU - Kruk, Marcin
AU - van Leeuwen, Hans
AU - Mavilia, Carmelo
AU - van Meurs, Joyce
AU - Mangion, Jon
AU - McGuigan, Fiona E.A.
AU - Pols, Huib
AU - Renner, Wilfried
AU - Rivadeneira, Fernando
AU - van Schoor, Natasja M.
AU - Scollen, Serena
AU - Sherlock, Rachael E.
AU - Ioannidis, John P.A.
N1 - © 2006 American College of Physicians
PY - 2006/8/15
Y1 - 2006/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33747115419&partnerID=8YFLogxK
U2 - 10.7326/0003-4819-145-4-200608150-00005
DO - 10.7326/0003-4819-145-4-200608150-00005
M3 - Article
C2 - 16908916
SN - 0003-4819
VL - 145
SP - 255
EP - 264
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 4
ER -