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

APOSS investigators; EPOS investigators; EPOLOS investigators; FAMOS investigators; LASA investigators; Rotterdam Study investigators; André 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; Y (Yue) Fang; Elzbieta Karczmarewicz; Marcin Kruk; Hans van Leeuwen; Carmelo Mavilia; Joyce van Meurs; Jon Mangion; Fiona E.A. McGuigan; Huib Pols; Wilfried Renner; Fernando Rivadeneira; Natasja M. van Schoor; Serena Scollen; Rachael E. Sherlock; John P.A. Ioannidis

doi:10.7326/0003-4819-145-4-200608150-00005

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

APOSS investigators
, EPOS investigators
, EPOLOS investigators
, FAMOS investigators
, LASA investigators
, Rotterdam Study investigators
, André 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, Y (Yue) Fang, Elzbieta Karczmarewicz, Marcin Kruk, Hans van Leeuwen, Carmelo Mavilia, Joyce van Meurs, Jon Mangion, Fiona E.A. McGuigan, Huib Pols, Wilfried Renner, Fernando Rivadeneira, Natasja M. van Schoor, Serena Scollen, Rachael E. Sherlock, John P.A. Ioannidis

Internal Medicine

University of Edinburgh
University of Florence
Oxagen Limited
University of Barcelona
Aarhus University Hospital
VU University Medical Center
Children's Memorial Health Institute
Medical University of Graz
University of Cambridge
University of Aberdeen School of Medicine, Medical Sciences and Nutrition
Hospital del Mar Medical Research Institute (IMIM)
University of Ioannina Medical School
Foundation for Research and Technology-Hellas

Research output: Contribution to journal › Article › Academic › peer-review

240 Citations (Scopus)

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.

Original language	English
Pages (from-to)	255-264
Number of pages	10
Journal	Annals of Internal Medicine
Volume	145
Issue number	4
DOIs	https://doi.org/10.7326/0003-4819-145-4-200608150-00005
Publication status	Published - 15 Aug 2006

Bibliographical note

Research programs

EMC MM-01-39-02
EMC NIHES-01-64-02
EMC OR-01-25-01

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10.7326/0003-4819-145-4-200608150-00005

Cite this

APOSS investigators, EPOS investigators, EPOLOS investigators, FAMOS investigators, LASA investigators, Rotterdam Study investigators, Uitterlinden, A., Ralston, S. H., Brandi, M. L., Carey, A. H., Grinberg, D., Langdahl, B. L., Lips, P., Lorenc, R., Obermayer-Pietsch, B., Reeve, J., Reid, D. M., Amedei, A., Bassiti, A., ... Ioannidis, J. P. A. (2006). The association between common vitamin D receptor gene variations and osteoporosis: A participant-level meta-analysis. Annals of Internal Medicine, 145(4), 255-264. https://doi.org/10.7326/0003-4819-145-4-200608150-00005

@article{217578aa567d4a5980622c2c4f5fb9de,

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. 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.",

author = "\{APOSS investigators\} and \{EPOS investigators\} and \{EPOLOS investigators\} and \{FAMOS investigators\} and \{LASA investigators\} and \{Rotterdam Study investigators\} and Andr{\'e} Uitterlinden and Ralston, \{Stuart H.\} and Brandi, \{Maria Luisa\} and Carey, \{Alisoun H.\} and Daniel Grinberg and Langdahl, \{Bente L.\} and Paul Lips and Roman Lorenc and Barbara Obermayer-Pietsch and Jonathan Reeve and Reid, \{David M.\} and Antonietta Amedei and Amelia Bassiti and Mariona Bustamante and Husted, \{Lise Bjerre\} and Adolfo Diez-Perez and Harald Dobnig and Dunning, \{Alison M.\} and Anna Enjuanes and Astrid Fahrleitner-Pammer and Fang, \{Y (Yue)\} and Elzbieta Karczmarewicz and Marcin Kruk and \{van Leeuwen\}, Hans and Carmelo Mavilia and \{van Meurs\}, Joyce and Jon Mangion and McGuigan, \{Fiona E.A.\} and Huib Pols and Wilfried Renner and Fernando Rivadeneira and \{van Schoor\}, \{Natasja M.\} and Serena Scollen and Sherlock, \{Rachael E.\} and Ioannidis, \{John P.A.\}",

note = "{\textcopyright} 2006 American College of Physicians",

year = "2006",

month = aug,

day = "15",

doi = "10.7326/0003-4819-145-4-200608150-00005",

language = "English",

volume = "145",

pages = "255--264",

journal = "Annals of Internal Medicine",

issn = "0003-4819",

publisher = "American College of Physicians",

number = "4",

}

APOSS investigators, EPOS investigators, EPOLOS investigators, FAMOS investigators, LASA investigators, Rotterdam Study investigators, Uitterlinden, A, Ralston, SH, Brandi, ML, Carey, AH, Grinberg, D, Langdahl, BL, Lips, P, Lorenc, R, Obermayer-Pietsch, B, Reeve, J, Reid, DM, Amedei, A, Bassiti, A, Bustamante, M, Husted, LB, Diez-Perez, A, Dobnig, H, Dunning, AM, Enjuanes, A, Fahrleitner-Pammer, A, Fang, Y, Karczmarewicz, E, Kruk, M, van Leeuwen, H, Mavilia, C, van Meurs, J, Mangion, J, McGuigan, FEA, Pols, H, Renner, W, Rivadeneira, F, van Schoor, NM, Scollen, S, Sherlock, RE & Ioannidis, JPA 2006, 'The association between common vitamin D receptor gene variations and osteoporosis: A participant-level meta-analysis', Annals of Internal Medicine, vol. 145, no. 4, pp. 255-264. https://doi.org/10.7326/0003-4819-145-4-200608150-00005

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.

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 - https://www.scopus.com/pages/publications/33747115419

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 -

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

Abstract

Bibliographical note

Research programs

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