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Two Polymorphisms in the Vitamin D Receptor Gene—Association With Bone Mass and 5‐Year Change in Bone Mass With or Without Hormone‐Replacement Therapy in Postmenopausal Women: The Danish Osteoporosis Prevention Study
Author(s) -
Tofteng C. L.,
Jensen J. E. B.,
Abrahamsen B.,
Odum L.,
Brot C.
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.8.1535
Subject(s) - medicine , calcitriol receptor , foki , endocrinology , osteoporosis , overweight , bone mineral , vitamin d and neurology , body mass index , hormone replacement therapy (female to male) , bone density , genotype , polymorphism (computer science) , testosterone (patch) , biology , genetics , gene
The significance of an interrelation between nongenetic factors and genotype effects in the regulation of bone mass is not clear. In this prospective study of 429 healthy early postmenopausal Danish women, we investigated the association between bone mineral density (BMD) and the Fok I and Bsm I polymorphisms in the vitamin D receptor (VDR) gene. Participants were allocated to either hormone‐replacement therapy (HRT) or no treatment by randomization or personal choice. After 5 years, 332 women with unchanged treatment status were available for analyses, 98 of these women were still on HRT. No association with initial BMD or 5‐year change in BMD was found for either polymorphism. In women with body mass index (BMI) < 25 ( n = 282), the f allele was associated with lower BMD of the hip ( p < 0.001) and forearm ( p = 0.001), and the b allele was associated with lower spine BMD ( p = 0.02). Comparing thin/normal weight women with overweight/obese women of the same genotype, FF women had similar BMD at all measured sites in contrast to Ff and ff women in whom BMD, as expected, was higher in the overweight/obese women. Similar results were found for the Bsm I polymorphism with no difference in BMD between BMI groups in BB women. Segregation into groups according to dietary calcium intake did not reveal any genotype association with BMD. These results provide some evidence of a modifying effect of nongenetic factors, specifically BMI, on the association between VDR genotype and BMD. High BMI may protect against lower BMD seen in association with the f or b alleles. In some genotypes ( FF and BB ), BMI had relatively little effect on BMD.