Journal Mobile Options
Table of Contents
Vol. 13, No. 5, 2004
Issue release date: September–October 2004
Open Access Gateway
Med Princ Pract 2004;13:260–266
(DOI:10.1159/000079524)

Vitamin D Receptor Alleles, Bone Mineral Density and Turnover in Postmenopausal Osteoporotic and Healthy Women

Duman B.S.a · Tanakol R.b · Erensoy N.c · Öztürk M.c · Yilmazer S.c
aDepartment of Medical Biology and Genetics, Kadir Has University Medical Faculty, Gayrettepe-Istanbul, and Departments of bEndocrinology and Metabolism and cMedical Biology, Istanbul University Faculty of Medicine, Çapa-Istanbul, Istanbul, Turkey
email Corresponding Author

Abstract

Objective: Vitamin D receptor (VDR) gene polymorphisms and bone metabolic markers were investigated as potential genetic markers for osteoporosis in postmenopausal Turkish women. The relationship between their VDR gene polymorphisms and bone states was determined. Materials and Methods: Restriction fragment length polymorphisms at the VDR gene locus (i.e., for BsmI, ApaI, and TaqI) was investigated in 75 postmenopausal osteoporotic (53.16 ± 1.31 years) and 66 healthy (52.62 ± 1.69 years) Turkish women and the genotypes were related to bone mineral density (BMD) at femoral neck (FN), lumbar spine (L1–4), trochanter, Ward’s triangle (Ward’s) and metabolic parameters of bone turnover. Results: In osteoporotic women, TaqI genotype-related differences of the VDR gene were found to be significant at all BMD sites; TT genotype had higher L1–4 BMD values than Tt and tt (p < 0.05); tt genotype had significantly lower BMD at FN (p < 0.05), trochanter (p < 0.01), and Ward’s (p < 0.05) compared to TT genotype. The tt genotype was found to be associated with higher (p < 0.05) serum osteocalcin levels compared to Tt and TT genotypes in the osteoporotic women, whereas no such association was found for the healthy women. Conclusion: Our data showed an association between VDR TaqI genotype and BMD at the FN, L1–4, trochanter and Ward’s triangle in nonobese postmenopausal osteoporotic women. Thus the VDR gene Taql polymorphism modulates differences in BMD in the postmenopausal osteoporotic women.


 goto top of outline Key Words

  • Bone mineral density
  • Vitamin D receptor gene polymorphism
  • Osteoporosis
  • Menopause

 goto top of outline Abstract

Objective: Vitamin D receptor (VDR) gene polymorphisms and bone metabolic markers were investigated as potential genetic markers for osteoporosis in postmenopausal Turkish women. The relationship between their VDR gene polymorphisms and bone states was determined. Materials and Methods: Restriction fragment length polymorphisms at the VDR gene locus (i.e., for BsmI, ApaI, and TaqI) was investigated in 75 postmenopausal osteoporotic (53.16 ± 1.31 years) and 66 healthy (52.62 ± 1.69 years) Turkish women and the genotypes were related to bone mineral density (BMD) at femoral neck (FN), lumbar spine (L1–4), trochanter, Ward’s triangle (Ward’s) and metabolic parameters of bone turnover. Results: In osteoporotic women, TaqI genotype-related differences of the VDR gene were found to be significant at all BMD sites; TT genotype had higher L1–4 BMD values than Tt and tt (p < 0.05); tt genotype had significantly lower BMD at FN (p < 0.05), trochanter (p < 0.01), and Ward’s (p < 0.05) compared to TT genotype. The tt genotype was found to be associated with higher (p < 0.05) serum osteocalcin levels compared to Tt and TT genotypes in the osteoporotic women, whereas no such association was found for the healthy women. Conclusion: Our data showed an association between VDR TaqI genotype and BMD at the FN, L1–4, trochanter and Ward’s triangle in nonobese postmenopausal osteoporotic women. Thus the VDR gene Taql polymorphism modulates differences in BMD in the postmenopausal osteoporotic women.

Copyright © 2004 S. Karger AG, Basel


 goto top of outline References
  1. Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S: Genetic determinants of bone mass in adults. J Clin Invest 1987;80:706–710.
  2. Christian JC, Yu PL, Slemenda CW, Johnston CC: Heritability of bone mass: A longitudinal study in aging male twins. Am J Hum Genet 1989;44:429–433.
  3. Smith DM, Nance WE, Kang KW, Christian JC, Johnston CC Jr: Genetic factors in determining bone mass. J Clin Invest 1973;52:2800–2808.
  4. 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 1987;8:207–209.
  5. Kelly PJ, Hopper JL, Macaskill GT, Pocock NA, Sambrook PN, Eisman JA: Genetic factors in bone turnover. J Clin Endocrinol Metab 1991;72:808–813.
  6. Lutz J: Bone mineral, serum calcium and dietary intakes of mother/daughter pairs. Am J Clin Nutr 1986;44:99–106.
  7. Seeman E, Hopper JL, Bach LA, Cooper ME, Parkinson E, McKay J, Jerums G: Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 1989;320:554–558.
  8. Morrison NA, Yeoman R, Kelly PJ, Eisman JA: Contribution of trans-acting factor alleles to normal physiological variability: Vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci USA 1992;89:6665–6669.
  9. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA: Prediction of bone density from vitamin D receptor alleles. Nature 1994;367:284–287.
  10. Eisman JA, Morrison NA, Kelly PJ, Sambrook PN, Howard G, Qi J, Tokita A, Crofts L, Nguyen TV, Birmingham J: Genetics of osteoporosis and vitamin D receptor alleles. Calcif Tissue Int 1995;56:S48–49.
  11. Peacock M: Vitamin D receptor gene alleles and osteoporosis: A contrasting view. J Bone Miner Res 1995;10:1294–1297.
  12. Yamagata Z, Miyamura T, Iijima S, Asaka A, Sasaki M, Kato J, Koizumi K: Vitamin D receptor gene polymorphism and bone mineral density in healthy Japanese women. Lancet 1994;344:1027.
  13. Krall EA, Parry P, Lichter JB, Dawson-Hughes B: Vitamin D receptor alleles and rates of bone loss: Influences of years since menopause and calcium intake. J Bone Miner Res 1995;10:978–984.
  14. Ferrari S, Rizzoli R, Chevalley T, Slosman D, Eisman JA, Bonjour J-P: Vitamin D receptor gene polymorphisms and chance in lumbar spine bone mineral density. Lancet 1995;345:423–424.
  15. Spector TD, Keen RW, Arden NK, Morrison NA, Major PJ, Nguyen TV, Kelly PJ, Baker JR, Sambrook PN, Lanchbury JS, Eisman JA: Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: A twin study in Britain. BMJ 1995;310:1357–1360.
  16. Fleet JC, Harris SS, Wood RJ, Dawson-Hughes B: The BsmI vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women. J Bone Miner Res 1995;10:985–990.
  17. Riggs BL, Nguyen TV, Melton LJ 3rd, Morrison NA, O’Fallon WM, Kelly PJ, Egan KS, Sambrook PN, Muhs JM, Eisman JA: The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal osteoporotic women. J Bone Miner Res 1995;10:991–996.
  18. Garnero P, Borel O, Sornay-Rendu E, Delmas PD: Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women. J Bone Miner Res 1995;10:1283–1288.
  19. Keen RW, Major PJ, Lanchbury JS, Spector TD: Vitamin D receptor gene polymorphism and bone loss. Lancet 1995;345:990.

    External Resources

  20. Looney J, Yoon HK, Fischer SM, Farley SM, Farley JR, Wegedal JE, Baylink DJ: Lack of a high prevalence of the BB vitamin D receptor genotype in severely osteoporotic women. J Clin Endocrinol Metab 1995;80:2158–2162.
  21. Kroger H, Mahonen A, Ryhanen S, Turunen AM, Alhava E, Maenpaa P: Vitamin D receptor genotypes and bone mineral density. Lancet 1995;345:1238.

    External Resources

  22. Lim SK, Park YS, Park JM, Song YD, Lee EJ, Kim KR, Lee HC, Huh KB: Lack of association between vitamin D receptor genotypes and osteoporosis in Koreans. J Clin Endocrinol Metab 1995;80:3677–3681.
  23. Hustmyer FG, Peacock M, Hui S, Johnston CC, Christian J: Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus. J Clin Invest 1994;94:2130–2134.
  24. Parfitt A: Vitamin D receptor genotypes in osteoporosis. Lancet 1994;344:1580.
  25. Shiraki M, Eguchi H, Aoki C, Shiraki Y: Can allelic variations in vitamin D receptor gene predict bone densities and serum osteocalcin level in Japanese women. Bone 1995;16(suppl 1):84S.
  26. Ho KC, Pang C: Automated analysis of urinary hydroxyproline. Clin Chim Acta 1989;185:191–196.
  27. Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from nucleated cells. Nucleic Acids Res 1998;16:1215.
  28. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA: Primer directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487–491.
  29. Jones G, Nguyen TV, Sambrook PN, Kelly PJ, Eisman JA: Progressive loss of bone in the femoral neck in elderly people: Longitudinal findings from the Dubbo osteoporosis epidemiology study. Br Med J 1994;309:691–695.
  30. Poggi M, Aterini S, Nicastro L, Chiarugi V, Ruggiero M, Pacini S, Gulisaro M: Lack of association between body weight, bone mineral density and vitamin D receptor gene polymorphism in normal and osteoporotic women. Dis Markers 1999;15:221–227.
  31. Sheehan D, Bennett T, Cashman KD: An assessment of genetic markers as predictors of bone turnover in healthy adults. J Endocrinol Invest 2001;24:236–245.
  32. Dawson-Hughes B, Harris SS, Finneran S: Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotypes. J Clin Endocrinol Metab 1995;80:3657–3661.
  33. Kirschner MA, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N: Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 1990;70:473–479.
  34. Vandevyver C, Wylin T, Cassiman J, Raus J, Geusens P: Influence of the vitamin D receptor gene alleles on bone mineral density in postmenopausal and osteoporotic women. J Bone Miner Res 1997;12:241–247.

 goto top of outline Author Contacts

Selma Yılmazer
Department of Medical Biology, Cerrahpaşa Faculty of Medicine
Istanbul University, TR–34310 Cerrahpaşa-Istanbul (Turkey)
Tel. +90 212 588 48 00, ext. 2032, Fax +90 212 632 00 50
E-Mail selmayilmazer@mynet.com


 goto top of outline Article Information

Received: January 20, 2003
Revised: June 28, 2003
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 5, Number of References : 34


 goto top of outline Publication Details

Medical Principles and Practice
A Publication of the Academic Publications Council

Vol. 13, No. 5, Year 2004 (Cover Date: September-October 2004)

Journal Editor: Farida Al Awadi, Kuwait
ISSN: 1011–7571 (print), 1423–0151 (Online)

For additional information: http://www.karger.com/mpp


Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Objective: Vitamin D receptor (VDR) gene polymorphisms and bone metabolic markers were investigated as potential genetic markers for osteoporosis in postmenopausal Turkish women. The relationship between their VDR gene polymorphisms and bone states was determined. Materials and Methods: Restriction fragment length polymorphisms at the VDR gene locus (i.e., for BsmI, ApaI, and TaqI) was investigated in 75 postmenopausal osteoporotic (53.16 ± 1.31 years) and 66 healthy (52.62 ± 1.69 years) Turkish women and the genotypes were related to bone mineral density (BMD) at femoral neck (FN), lumbar spine (L1–4), trochanter, Ward’s triangle (Ward’s) and metabolic parameters of bone turnover. Results: In osteoporotic women, TaqI genotype-related differences of the VDR gene were found to be significant at all BMD sites; TT genotype had higher L1–4 BMD values than Tt and tt (p < 0.05); tt genotype had significantly lower BMD at FN (p < 0.05), trochanter (p < 0.01), and Ward’s (p < 0.05) compared to TT genotype. The tt genotype was found to be associated with higher (p < 0.05) serum osteocalcin levels compared to Tt and TT genotypes in the osteoporotic women, whereas no such association was found for the healthy women. Conclusion: Our data showed an association between VDR TaqI genotype and BMD at the FN, L1–4, trochanter and Ward’s triangle in nonobese postmenopausal osteoporotic women. Thus the VDR gene Taql polymorphism modulates differences in BMD in the postmenopausal osteoporotic women.



 goto top of outline Author Contacts

Selma Yılmazer
Department of Medical Biology, Cerrahpaşa Faculty of Medicine
Istanbul University, TR–34310 Cerrahpaşa-Istanbul (Turkey)
Tel. +90 212 588 48 00, ext. 2032, Fax +90 212 632 00 50
E-Mail selmayilmazer@mynet.com


 goto top of outline Article Information

Received: January 20, 2003
Revised: June 28, 2003
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 5, Number of References : 34


 goto top of outline Publication Details

Medical Principles and Practice
A Publication of the Academic Publications Council

Vol. 13, No. 5, Year 2004 (Cover Date: September-October 2004)

Journal Editor: Farida Al Awadi, Kuwait
ISSN: 1011–7571 (print), 1423–0151 (Online)

For additional information: http://www.karger.com/mpp


Open Access License / Drug Dosage

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S: Genetic determinants of bone mass in adults. J Clin Invest 1987;80:706–710.
  2. Christian JC, Yu PL, Slemenda CW, Johnston CC: Heritability of bone mass: A longitudinal study in aging male twins. Am J Hum Genet 1989;44:429–433.
  3. Smith DM, Nance WE, Kang KW, Christian JC, Johnston CC Jr: Genetic factors in determining bone mass. J Clin Invest 1973;52:2800–2808.
  4. 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 1987;8:207–209.
  5. Kelly PJ, Hopper JL, Macaskill GT, Pocock NA, Sambrook PN, Eisman JA: Genetic factors in bone turnover. J Clin Endocrinol Metab 1991;72:808–813.
  6. Lutz J: Bone mineral, serum calcium and dietary intakes of mother/daughter pairs. Am J Clin Nutr 1986;44:99–106.
  7. Seeman E, Hopper JL, Bach LA, Cooper ME, Parkinson E, McKay J, Jerums G: Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 1989;320:554–558.
  8. Morrison NA, Yeoman R, Kelly PJ, Eisman JA: Contribution of trans-acting factor alleles to normal physiological variability: Vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci USA 1992;89:6665–6669.
  9. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA: Prediction of bone density from vitamin D receptor alleles. Nature 1994;367:284–287.
  10. Eisman JA, Morrison NA, Kelly PJ, Sambrook PN, Howard G, Qi J, Tokita A, Crofts L, Nguyen TV, Birmingham J: Genetics of osteoporosis and vitamin D receptor alleles. Calcif Tissue Int 1995;56:S48–49.
  11. Peacock M: Vitamin D receptor gene alleles and osteoporosis: A contrasting view. J Bone Miner Res 1995;10:1294–1297.
  12. Yamagata Z, Miyamura T, Iijima S, Asaka A, Sasaki M, Kato J, Koizumi K: Vitamin D receptor gene polymorphism and bone mineral density in healthy Japanese women. Lancet 1994;344:1027.
  13. Krall EA, Parry P, Lichter JB, Dawson-Hughes B: Vitamin D receptor alleles and rates of bone loss: Influences of years since menopause and calcium intake. J Bone Miner Res 1995;10:978–984.
  14. Ferrari S, Rizzoli R, Chevalley T, Slosman D, Eisman JA, Bonjour J-P: Vitamin D receptor gene polymorphisms and chance in lumbar spine bone mineral density. Lancet 1995;345:423–424.
  15. Spector TD, Keen RW, Arden NK, Morrison NA, Major PJ, Nguyen TV, Kelly PJ, Baker JR, Sambrook PN, Lanchbury JS, Eisman JA: Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: A twin study in Britain. BMJ 1995;310:1357–1360.
  16. Fleet JC, Harris SS, Wood RJ, Dawson-Hughes B: The BsmI vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women. J Bone Miner Res 1995;10:985–990.
  17. Riggs BL, Nguyen TV, Melton LJ 3rd, Morrison NA, O’Fallon WM, Kelly PJ, Egan KS, Sambrook PN, Muhs JM, Eisman JA: The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal osteoporotic women. J Bone Miner Res 1995;10:991–996.
  18. Garnero P, Borel O, Sornay-Rendu E, Delmas PD: Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women. J Bone Miner Res 1995;10:1283–1288.
  19. Keen RW, Major PJ, Lanchbury JS, Spector TD: Vitamin D receptor gene polymorphism and bone loss. Lancet 1995;345:990.

    External Resources

  20. Looney J, Yoon HK, Fischer SM, Farley SM, Farley JR, Wegedal JE, Baylink DJ: Lack of a high prevalence of the BB vitamin D receptor genotype in severely osteoporotic women. J Clin Endocrinol Metab 1995;80:2158–2162.
  21. Kroger H, Mahonen A, Ryhanen S, Turunen AM, Alhava E, Maenpaa P: Vitamin D receptor genotypes and bone mineral density. Lancet 1995;345:1238.

    External Resources

  22. Lim SK, Park YS, Park JM, Song YD, Lee EJ, Kim KR, Lee HC, Huh KB: Lack of association between vitamin D receptor genotypes and osteoporosis in Koreans. J Clin Endocrinol Metab 1995;80:3677–3681.
  23. Hustmyer FG, Peacock M, Hui S, Johnston CC, Christian J: Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus. J Clin Invest 1994;94:2130–2134.
  24. Parfitt A: Vitamin D receptor genotypes in osteoporosis. Lancet 1994;344:1580.
  25. Shiraki M, Eguchi H, Aoki C, Shiraki Y: Can allelic variations in vitamin D receptor gene predict bone densities and serum osteocalcin level in Japanese women. Bone 1995;16(suppl 1):84S.
  26. Ho KC, Pang C: Automated analysis of urinary hydroxyproline. Clin Chim Acta 1989;185:191–196.
  27. Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from nucleated cells. Nucleic Acids Res 1998;16:1215.
  28. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA: Primer directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487–491.
  29. Jones G, Nguyen TV, Sambrook PN, Kelly PJ, Eisman JA: Progressive loss of bone in the femoral neck in elderly people: Longitudinal findings from the Dubbo osteoporosis epidemiology study. Br Med J 1994;309:691–695.
  30. Poggi M, Aterini S, Nicastro L, Chiarugi V, Ruggiero M, Pacini S, Gulisaro M: Lack of association between body weight, bone mineral density and vitamin D receptor gene polymorphism in normal and osteoporotic women. Dis Markers 1999;15:221–227.
  31. Sheehan D, Bennett T, Cashman KD: An assessment of genetic markers as predictors of bone turnover in healthy adults. J Endocrinol Invest 2001;24:236–245.
  32. Dawson-Hughes B, Harris SS, Finneran S: Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotypes. J Clin Endocrinol Metab 1995;80:3657–3661.
  33. Kirschner MA, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N: Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 1990;70:473–479.
  34. Vandevyver C, Wylin T, Cassiman J, Raus J, Geusens P: Influence of the vitamin D receptor gene alleles on bone mineral density in postmenopausal and osteoporotic women. J Bone Miner Res 1997;12:241–247.