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Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women

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Abstract

Polymorphism of vitamin D receptor (VDR) gene has been found to be associated with serum osteocalcin (OC) levels and bone mineral density (BMD) in Caucasian identical twins and unrelated postmenopausal women. Being ethnically different and living in a geographic area with adequate vitamin D status due to abundant sunshine exposure, it is unclear whether VDR gene polymorphism will affect bone mass in Thai population. In the present study, we investigated the association between VDR gene polymorphism and bone metabolism in Thai postmenopausal women. Subjects consisted of 84 postmenopausal women. Bsm I, Taq I and Apa I polymorphisms of VDR gene were determined by PCR-RFLP. B, T and A represent the absence of the corresponding restriction sites while b, t and a indicate the presence of the restriction sites. Data were expressed as mean ± SE. Sixty-six subjects (78.6%) had bb genotype while 18 (21.4%) had Bb genotype. None of the subjects was found to have BB genotype. Taq I restriction site was in linkage disequilibrium to the Bsm I site. For Apa I polymorphism, 33 (39.3%), 42 (50.0%) and 9 (10.7%) of the subjects had aa, Aa and AA genotypes, respectively. There was no significant difference in serum intact OC levels and BMD at various skeletal sites among subjects with different genotypes. Despite the lack of difference in BMD and intact OC levels, subjects with bb genotype had higher 24-hour urinary calcium excretion than those with Bb genotype (bb, 6.1 ±0.3 mmol/day; Bb, 4.4±0.6 mmol/day; p<0.05). The effect of Bsm I VDR genotype was still significant (p<0.05) after dietary calcium intake was controlled using analysis of covariance. Despite the difference in urinary calcium levels, there was no significant difference in fractional excretion of calcium among subjects with different Bsm I-related genotypes, suggesting that the effect of the VDR gene polymorphism on urinary calcium excretion is more likely due to the effect on intestinal calcium absorption rather than renal tubular calcium reabsorption. We conclude that VDR genotype distributions in Thai postmenopausal women are different from those reported in Caucasians. VDR gene polymorphism does not appear to be associated with BMD or bone turnover in Thai postmenopausal women. However, Bsm I VDR polymorphism may have physiologic role in calcium homeostatasis by modulating intestinal calcium absorption.

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References

  1. Moller M., Horsman A., Harvald B., Hauge M., Henningsen K., Nordin B.E.C. Metacarpal morphometry in monozygotic and dizygotic elderly twins. Calcif. Tissue Res. 25: 197, 1978.

    Article  PubMed  CAS  Google Scholar 

  2. Krall E.A., Dawson-Hughes B. Heritable and life-style determinants of bone mineral density. J. Bone. Miner. Res 8: 1, 1993.

    Article  PubMed  CAS  Google Scholar 

  3. Smith D.M., Nance W.E., Kang K.W., Christian J.C., Johnston C.C. Genetic factors in determining bone mass. J. Clin. Invest. 52: 2800, 1973.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Pocock N.A., Eisman J.A., Hopper J.L., Yeates M.G., Sambrook P.N., Eberl S. Genetic determinants of bone mass in adults. A twin study. J. Clin. Invest. 80: 706, 1987.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Dequeker J., Nijs J., Verstraeten A., Geusens P., Gevers G. Genetic determinants of bone mineral content at the spine and radius: A twin study. Bone 8: 207, 1987.

    Article  PubMed  CAS  Google Scholar 

  6. Slemenda C.W., Christian J.C., Reed T., Reister T.K., Williams C.J., Johnston C.C. Long-term bone loss in men: effects of genetic and environmental factors. Ann. Intern. Med. 117: 286, 1992.

    Article  PubMed  CAS  Google Scholar 

  7. Morrison N.A., Qi J.C., Tokita A., Kelly P.J., Crofts L., Nguyen T.V., Sambrook P. N., Eisman J.A. Prediction of bone density from vitamin D receptor alleles. Nature 367: 284, 1994.

    Article  PubMed  CAS  Google Scholar 

  8. Yamagata Z., Miyamura T., Iijima S., Asaka A., Sasaki M., Dato J., Koizumi K. Vitamin D receptor gene polymorphism and bone mineral density in healthy Japanese women. Lancet 344: 1027, 1994.

    Article  PubMed  CAS  Google Scholar 

  9. Lim S.K., Park Y.S., Park J.M., Song Y.D., Lee E.J., Kim K.R., Lee H.C., Huh K.B. Lack of association between vitamin D receptor genotypes and osteoporosis in Koreans. J. Clin. Endocrinol. Metab. 80: 3677, 1995.

    PubMed  CAS  Google Scholar 

  10. Chailurkit L., Rajatanavin R., Teerarungsikul K., Ongphiphadhanakul B. & Puavilai G. Vitamin D status, parathyroid hormone and biochemical marker of bone turnover in normal Thai subjects. J. Med. Assoc. Thai. 79: 499, 1996.

    PubMed  CAS  Google Scholar 

  11. Riggs B.L., Nguyen T.V., Melton III L.J., Morrison N.A., O’Fallon W.M., Kelly P.J., Egan K.S., Sambrook P.N., Muhs J.M., Eisman J.A. The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women. J. Bone Miner. Res. 10: 991, 1995.

    Article  PubMed  CAS  Google Scholar 

  12. Hustmyer F.G., DeLuca H.F., Peacock M. Apal, Bsml, Eco R.V. and Tagl polymorphisms at the human vitamin D receptor gene locus in Caucasians, blacks, and asians. Hum. Mol. Genet. 2: 487, 1993.

    Article  PubMed  CAS  Google Scholar 

  13. Peacock M. Vitamin D receptor gene alleles and osteoporosis: a contrasting view. J. Bone Miner. Res. 10: 1294, 1995.

    Article  PubMed  CAS  Google Scholar 

  14. Smith E.P., Boyd J., Frank G.R., Takahashi H., Cohen R.M., Specker B., Williams T.C., Lubahn D.B., Korach K.S. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med. 331: 1056, 1994.

    Article  PubMed  CAS  Google Scholar 

  15. Conte F.A., Grumbach M.M., Ito Y., Fisher C.R., Simpson E.R. A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutation in the gene encoding aromatase (P450arom). J. Clin. Endocrinol. Metab. 78: 1287, 1994.

    PubMed  CAS  Google Scholar 

  16. Spencer R., Charman M., Wilson P., Lawson D.E.M. Production and properties of vitamin D-induced mRNA for chick calcium-binding protein. Eur. J. Biochem. 71: 399, 1976.

    Article  PubMed  CAS  Google Scholar 

  17. Borke J.L., Caride A., Verma A.K., Penniston J.T., Kumar R. Plasma membrane calcium pump and 28-kDa calcium binding protein in cells of rat kidney distal tubules. Am. J. Physiol. 257: F842, 1989.

    PubMed  CAS  Google Scholar 

  18. Stumpf W.E., Sar M., Narbaitz R., Reid F.A., DeLuca H.F., Tanaka Y. Target cells for 1,25-dihydroxyvitamin D in intestinal tract, stomach, kidney, skin, pituitary and parathyroid. Proc. Natl. Acad. Sci. USA. 77: 1149, 1980.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Dawson-Hughes B., Harris S.S., Finneran S. Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotype. J. Clin. Endocrinol. Metab. 80: 3657, 1995.

    PubMed  CAS  Google Scholar 

  20. Howard G., Nguyen T., Morrison N., Watanabe T., Sambrook P., Eisman J., Kelly P. Genetic influences of bone density: physiological correlates of vitamin D receptor gene alleles in premenopausal women. J. Clin. Endocrinol. Metab. 80: 2800, 1995.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Mahidol University, Bangkok, Thailand

    B. Ongphiphadhanakul M.D., R. Rajatanavin, L. Chailurkit, N. Piaseu, K. Teerarungsikul, S. Komindr & G. Puavilai

  2. Research Center, Mahidol University, Bangkok, Thailand

    S. Chanprasertyothin

  3. Department of Radiology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    R. Sirisriro

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  1. B. Ongphiphadhanakul M.D.
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  2. R. Rajatanavin
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  3. S. Chanprasertyothin
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  4. L. Chailurkit
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  5. N. Piaseu
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  6. K. Teerarungsikul
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  7. R. Sirisriro
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  8. S. Komindr
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  9. G. Puavilai
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Ongphiphadhanakul, B., Rajatanavin, R., Chanprasertyothin, S. et al. Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women. J Endocrinol Invest 20, 592–596 (1997). https://doi.org/10.1007/BF03346915

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  • DOI: https://doi.org/10.1007/BF03346915

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