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

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; Antonietta Amidei; 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; APOSS Investigators

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

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, Antonietta Amidei, Amelia Bassiti, Mariona Bustamante, Lise Bjerre Husted, Adolfo Diez-Perez, Harald Dobnig, Alison M Dunning, Anna EnjuanesAstrid 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, APOSS Investigators

Orthopedics

Erasmus University Medical Center

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

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
Publication status	Published - 2006 Aug 15

Subject classification (UKÄ)

Orthopedics

Free 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

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http://www.annals.org/cgi/content/abstract/145/4/255

Cite this

Uitterlinden, A. G., 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., Amidei, A., Bassiti, A., Bustamante, M., Husted, L. B., Diez-Perez, A., Dobnig, H., Dunning, A. M., ... APOSS Investigators (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. http://www.annals.org/cgi/content/abstract/145/4/255

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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.",

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",

author = "Uitterlinden, {Andr{\'e} G} 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 Antonietta Amidei 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 Yue Fang and Elzbieta Karczmarewicz and Marcin Kruk and {van Leeuwen}, {Johannes P T M} and Carmelo Mavilia and {van Meurs}, {Joyce B J} and Jon Mangion and McGuigan, {Fiona E A} and Pols, {Huibert A P} and Wilfried Renner and Fernando Rivadeneira and {van Schoor}, {Natasja M} and Serena Scollen and Sherlock, {Rachael E} and Ioannidis, {John P A} and {APOSS Investigators}",

year = "2006",

month = aug,

day = "15",

language = "English",

volume = "145",

pages = "255--264",

journal = "Annals of Internal Medicine",

issn = "0003-4819",

publisher = "American College of Physicians",

number = "4",

}

Uitterlinden, AG, Ralston, SH, Brandi, ML, Carey, AH, Grinberg, D, Langdahl, BL, Lips, P, Lorenc, R, Obermayer-Pietsch, B, Reeve, J, Reid, DM, Amedei, A, Amidei, 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, JPTM, Mavilia, C, van Meurs, JBJ, Mangion, J, McGuigan, FEA, Pols, HAP, Renner, W, Rivadeneira, F, van Schoor, NM, Scollen, S, Sherlock, RE, Ioannidis, JPA & APOSS Investigators 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. <http://www.annals.org/cgi/content/abstract/145/4/255>

TY - JOUR

T1 - The association between common vitamin D receptor gene variations and osteoporosis

T2 - a participant-level meta-analysis

AU - Uitterlinden, André G

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 - Amidei, 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, Yue

AU - Karczmarewicz, Elzbieta

AU - Kruk, Marcin

AU - van Leeuwen, Johannes P T M

AU - Mavilia, Carmelo

AU - van Meurs, Joyce B J

AU - Mangion, Jon

AU - McGuigan, Fiona E A

AU - Pols, Huibert A P

AU - Renner, Wilfried

AU - Rivadeneira, Fernando

AU - van Schoor, Natasja M

AU - Scollen, Serena

AU - Sherlock, Rachael E

AU - Ioannidis, John P A

AU - APOSS Investigators

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.

KW - Adult

KW - Aged

KW - Bone Density

KW - CDX2 Transcription Factor

KW - Deoxyribonucleases, Type II Site-Specific

KW - Female

KW - Fractures, Bone

KW - Genotype

KW - Haplotypes

KW - Homeodomain Proteins

KW - Humans

KW - Male

KW - Middle Aged

KW - Osteoporosis

KW - Polymorphism, Genetic

KW - Promoter Regions, Genetic

KW - Prospective Studies

KW - Receptors, Calcitriol

KW - Journal Article

KW - Meta-Analysis

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

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

Subject classification (UKÄ)

Free keywords

Access to Document

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