Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women

Helen Margaret MacDonald, Fiona Elizabeth Anne McGuigan, Alison Stewart, A. J. Black, W. D. Fraser, S. H. Ralston, David M Reid

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Abstract

Introduction: Population studies of vitamin D receptor (VDR) polymorphisms have produced conflicting results. We performed a comprehensive study dealing with all potential confounders in a large population to determine whether polymorphisms in the VDR gene influence bone health.

Materials and Methods: We studied 3100 women (50-63 years old) with bone markers, 25-hydroxyvitamin D, calcium, PTH, diet, and physical activity collected in 1998-2000. BMD was measured in 1990-1994 and 1998-2000. Fracture prevalence was assessed in 2002. Women were genotyped for five polymorphisms in the VDR gene: Cdx-2, Fok1, Bsm1, Apa1, and Taq1. The relationship between VDR and BMD, and interactions between VDR genotype, dietary calcium, and 25-hydroxyvitamin D, were examined using analysis of covariance.

Results: Compared with carriers of the G allele, homozygotes for the rare Cdx-2 A polymorphisin (n = 136) had less bone loss (-0.5 +/- 1.2 versus -0.7 +/- 1.0%/year [SD]; p = 0.01) and lower PTH (3.0 +/- 1.6 versus 3.4 +/- 2.0 pM; p = 0.03) despite similar vitamin D status. The association was not significant after correction for multiple testing or adjustment for confounders. At low calcium intakes, AA homozygotes had greater femoral neck (FN) BMD compared with carriers of the G allele, but at higher calcium intakes, the association was reversed. At low calcium intake, homozygotes for the b allele of Bsm1 had greater BMD compared with carriers of the B allele, but at higher calcium intakes, there was no difference. Similar results were seen for the Taq1 polymorphism. There was no evidence of gene-nutrient interaction when adjusted for body weight. No interactions between genotypes and vitamin D status on BMD were observed.

Conclusions: VDR does not seem to influence BMD or bone turnover in early postmenopausal white women with adequate calcium intake. Gene-nutrient interactions on BMD may be an indirect consequence of interactions between genotype and calcium intake on weight.

Original languageEnglish
Pages (from-to)151-162
Number of pages11
JournalJournal of Bone and Mineral Research
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • vitamin D receptor
  • polymorphism
  • diet
  • calcium
  • postmenopausal women
  • bone-mineral density
  • D-receptor genotype
  • vitamin-D
  • haplotype reconstruction
  • calcium intake
  • fracture
  • rates
  • size
  • 25-hydroxyvitamin-D
  • standardization

Cite this

Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women. / MacDonald, Helen Margaret; McGuigan, Fiona Elizabeth Anne; Stewart, Alison; Black, A. J.; Fraser, W. D.; Ralston, S. H.; Reid, David M.

In: Journal of Bone and Mineral Research, Vol. 21, No. 1, 01.2006, p. 151-162.

Research output: Contribution to journalArticle

MacDonald, Helen Margaret ; McGuigan, Fiona Elizabeth Anne ; Stewart, Alison ; Black, A. J. ; Fraser, W. D. ; Ralston, S. H. ; Reid, David M. / Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women. In: Journal of Bone and Mineral Research. 2006 ; Vol. 21, No. 1. pp. 151-162.
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T1 - Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women

AU - MacDonald, Helen Margaret

AU - McGuigan, Fiona Elizabeth Anne

AU - Stewart, Alison

AU - Black, A. J.

AU - Fraser, W. D.

AU - Ralston, S. H.

AU - Reid, David M

PY - 2006/1

Y1 - 2006/1

N2 - Introduction: Population studies of vitamin D receptor (VDR) polymorphisms have produced conflicting results. We performed a comprehensive study dealing with all potential confounders in a large population to determine whether polymorphisms in the VDR gene influence bone health.Materials and Methods: We studied 3100 women (50-63 years old) with bone markers, 25-hydroxyvitamin D, calcium, PTH, diet, and physical activity collected in 1998-2000. BMD was measured in 1990-1994 and 1998-2000. Fracture prevalence was assessed in 2002. Women were genotyped for five polymorphisms in the VDR gene: Cdx-2, Fok1, Bsm1, Apa1, and Taq1. The relationship between VDR and BMD, and interactions between VDR genotype, dietary calcium, and 25-hydroxyvitamin D, were examined using analysis of covariance.Results: Compared with carriers of the G allele, homozygotes for the rare Cdx-2 A polymorphisin (n = 136) had less bone loss (-0.5 +/- 1.2 versus -0.7 +/- 1.0%/year [SD]; p = 0.01) and lower PTH (3.0 +/- 1.6 versus 3.4 +/- 2.0 pM; p = 0.03) despite similar vitamin D status. The association was not significant after correction for multiple testing or adjustment for confounders. At low calcium intakes, AA homozygotes had greater femoral neck (FN) BMD compared with carriers of the G allele, but at higher calcium intakes, the association was reversed. At low calcium intake, homozygotes for the b allele of Bsm1 had greater BMD compared with carriers of the B allele, but at higher calcium intakes, there was no difference. Similar results were seen for the Taq1 polymorphism. There was no evidence of gene-nutrient interaction when adjusted for body weight. No interactions between genotypes and vitamin D status on BMD were observed.Conclusions: VDR does not seem to influence BMD or bone turnover in early postmenopausal white women with adequate calcium intake. Gene-nutrient interactions on BMD may be an indirect consequence of interactions between genotype and calcium intake on weight.

AB - Introduction: Population studies of vitamin D receptor (VDR) polymorphisms have produced conflicting results. We performed a comprehensive study dealing with all potential confounders in a large population to determine whether polymorphisms in the VDR gene influence bone health.Materials and Methods: We studied 3100 women (50-63 years old) with bone markers, 25-hydroxyvitamin D, calcium, PTH, diet, and physical activity collected in 1998-2000. BMD was measured in 1990-1994 and 1998-2000. Fracture prevalence was assessed in 2002. Women were genotyped for five polymorphisms in the VDR gene: Cdx-2, Fok1, Bsm1, Apa1, and Taq1. The relationship between VDR and BMD, and interactions between VDR genotype, dietary calcium, and 25-hydroxyvitamin D, were examined using analysis of covariance.Results: Compared with carriers of the G allele, homozygotes for the rare Cdx-2 A polymorphisin (n = 136) had less bone loss (-0.5 +/- 1.2 versus -0.7 +/- 1.0%/year [SD]; p = 0.01) and lower PTH (3.0 +/- 1.6 versus 3.4 +/- 2.0 pM; p = 0.03) despite similar vitamin D status. The association was not significant after correction for multiple testing or adjustment for confounders. At low calcium intakes, AA homozygotes had greater femoral neck (FN) BMD compared with carriers of the G allele, but at higher calcium intakes, the association was reversed. At low calcium intake, homozygotes for the b allele of Bsm1 had greater BMD compared with carriers of the B allele, but at higher calcium intakes, there was no difference. Similar results were seen for the Taq1 polymorphism. There was no evidence of gene-nutrient interaction when adjusted for body weight. No interactions between genotypes and vitamin D status on BMD were observed.Conclusions: VDR does not seem to influence BMD or bone turnover in early postmenopausal white women with adequate calcium intake. Gene-nutrient interactions on BMD may be an indirect consequence of interactions between genotype and calcium intake on weight.

KW - vitamin D receptor

KW - polymorphism

KW - diet

KW - calcium

KW - postmenopausal women

KW - bone-mineral density

KW - D-receptor genotype

KW - vitamin-D

KW - haplotype reconstruction

KW - calcium intake

KW - fracture

KW - rates

KW - size

KW - 25-hydroxyvitamin-D

KW - standardization

U2 - 10.1359/JBMR.050906

DO - 10.1359/JBMR.050906

M3 - Article

VL - 21

SP - 151

EP - 162

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 1

ER -