Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women.
The VDR is a candidate gene for osteoporosis. Here we studied five common polymorphisms of VDR in relation to calcium intake and vitamin D status in a population-based cohort of 3100 British women, but found no significant association with bone mass, bone loss, or fracture.


BACKGROUND
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.


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 polymorphism (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.
Macdonald
Helen M
HM
Department of Medicine and Therapeutics, University of Aberdeen, Medical School Buildings, Foresterhill, Aberdeen, United Kingdom. h.macdonald@abdn.ac.uk
McGuigan
Fiona E
FE
Stewart
Alison
A
Black
Alison J
AJ
Fraser
William D
WD
Ralston
Stuart
S
Reid
David M
DM
D000483:Alleles; D015519:Bone Density / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics* / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D018167:Receptors, Calcitriol / Q000235:genetics*; D006113:United Kingdom; D014807:Vitamin D / Q000378:metabolism
D018167:Receptors, Calcitriol; D014807:Vitamin D; D002118:Calcium