Association of vitamin D receptor gene polymorphism with a bone mineral density level in postmenopausal women
https://doi.org/10.29235/1814-6023-2019-16-2-192-201
Abstract
The analysis of association of polymorphic variants of the vitamin D receptor gene (VDR) with bone mineral density (BMD) values in menopausal women was performed. The study included 66 patients with postmenopausal osteoporosis (PMO group) and 170 postmenopausal women with normal BMD values (CON group). The statistically significant difference between the analyzed groups in the genotypes and the alleles frequency distribution for the VDR ApaI gene variant was revealed: for the carriers of C/C genotype, the risk of osteoporosis was higher compared to individuals with A/A genotype (OR = 2.7 [95 % CI: 1.5–4.7], p = 0.002). Allele A was overrepresented in the CON group and associated with the reduced risk of disease (OR = 0.6 [95 % CI: 0.4–0.8], p = 0.001). Statistically significant differences were found between the studied groups when analyzing VDR BsmI gene variant distribution. For the individuals with the unfavorable VDR BsmI G/G-genotype, the risk of PMO was significantly higher when compared to the carriers of the A/A-genotype (OR = 2.1 [95 % CI: 1.0–4.4], p = 0.02). For the bearers of A-allele, the risk of osteoporosis was significantly lower (OR = 0.6 [95 % CI: 0.4–0.9], p = 0.007). Among the carriers of the VDR ApaI C/C-genotype, the average BMD level was by 13.7 % lower compared to the carriers of the VDR ApaI A/A-genotype (0.767 and 0.872 g/cm2, respectively, p = 0.04); among individuals with the TaqI C/C-genotype, the BMD level was by 13.8 % lower compared to TaqI T/T-genotype bearers (0.803 and 0.914 g/cm2, respectively, p = 0.03).
VDR gene polymorphism may play an important role in the susceptibility to osteoporosis and is significantly associated with the BMD level in postmenopausal women.
About the Authors
A. V. Rudenka
Belarusian Medical Academy of Postgraduate Education
Belarus
Belarus
Alena V. Rudenka – Ph. D. (Med.), Assistant professor
3/3, P. Browka Str., 220013, Minsk
E. V. Rudenka
Belarusian State Medical University
Belarus
Belarus
Ema V. Rudenka – D. Sc. (Med.), Professor
83, Dzerzhinski Ave., 220116, Minsk
V. Yu. Samokhovec
Minsk City Center for Osteoporosis and Bone-Muscular Diseases Prevention
Belarus
Belarus
Volha Yu. Samokhovec – Ph. D. (Med.), Doctor
Minsk
K. V. Kobets
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus
Belarus
Belarus
Katsiaryna V. Kobets – Junior Researcher
27, Akademicheskaya Str., 220072, Minsk
P. M. Marozik
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus
Belarus
Belarus
Pavel M. Marozik – Ph. D. (Med.), Assistant professor, Leading researcher
27, Akademicheskaya Str., 220072, Minsk
References
1. Christakos S., Dhawan P., Porta A., Mady L. J., Seth T. Vitamin D and intestinal calcium absorption. Molecular and Cellular Endocrinology, 2011, vol. 347, no. 1–2, pp. 25–29. https://doi.org/10.1016/j.mce.2011.05.038
2. Hoenderop J. G., Müller D., van der Kemp A. W., Hartog A., Suzuki M., Ishibashi K., Imai M., Sweep F., Willems P. H., van Os C. H., Bindels R. J. Calcitriol controls the epithelial calcium channel in kidney. Journal of the American Society of Nephrology, 2001, vol. 12, pp. 1342–1349.
3. Myamoto K.-i., Kesterson R. A., Yamamoto H., Taketani Y., Nishiwaki E., Tatsumi S., Inoue Y., Morita K., Takeda E., Pike J. W. Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Molecular Endocrinology, 1997, vol. 11, no. 8, pp. 1165–1179. https://doi.org/10.1210/me.11.8.1165
4. Yamamoto H., Miyamoto K., Li B., Taketani Y., Kitano M., Inoue Y. [et al.]. The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine. Journal of Bone and Mineral Research, 1999, vol. 14, no. 2, pp. 240–247. https://doi.org/10.1359/jbmr.1999.14.2.240
5. Arai H., Miyamoto K.-I., Yoshida M., Yamamoto H., Taketani Y., Morita K. [et al.]. The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. Journal of Bone and Mineral Research, 2001, vol. 16, no. 7, pp. 1256–1264. https://doi.org/10.1359/jbmr.2001.16.7.1256
6. Fang Y., van Meurs Joyce B. J., Bergink A. P., Hofman A., van Duijn C. M., van Leeuwen J. P., P. Pols H. A., Uitterlinden A. G. Cdx-2 polymorphism in the promoter region of the human vitamin D receptor gene determines susceptibility to fracture in the elderly. Journal of Bone and Mineral Research, 2003, vol. 18, no. 9, pp. 1632–1641. https://doi.org/10.1359/jbmr.2003.18.9.1632
7. Gross C., Krishnan A. V., Malloy P. J., Eccleshall T. R., Zhao X.-Y., Feldman D. The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI variants. Journal of Bone and Mineral Research, 1998, vol. 13, no. 11, pp. 1691–1699. https://doi.org/10.1359/jbmr.1998.13.11.1691
8. Zmuda J. M., Cauley J. A., Ferrell R. E. Molecular epidemiology of vitamin D receptor gene variants. Epidemiologic Reviews, 2000, vol. 22, no. 2, pp. 203–217. https://doi.org/10.1093/oxfordjournals.epirev.a018033
9. Lips P. Vitamin D defciency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocrine Reviews, 2001, vol. 22, no. 4, pp. 477–501. https://doi.org/10.1210/er.22.4.477
10. Garnero P., Munoz F., Borel O., Sornay-Rendu E., Delmas P. D. Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density. The OFELY study. Journal of Clinical Endocrinology and Metabolism, 2005, vol. 90, no. 8, pp. 4829–4835. https://doi.org/10.1210/jc.2005-0364
11. Jurutka P. W., Whitfeld G. K., Hsieh J. C., Thompson P. D., Haussler C. A., Haussler M. R. Molecular nature of the vitamin D receptor and its role in regulation of gene expression. Reviews in Endocrine and Metabolic Disorders, 2001, vol. 2, no. 2, pp. 203–216.
12. Li Y., Xi B., Li K., Wang C. Association between vitamin D receptor gene polymorphisms and bone mineral density in Chinese women. Molecular Biology Reports, 2012, vol. 39, no. 5, pp. 5709–5717. https://doi.org/10.1007/s11033-011-1380-3
13. Pouresmaeili F., Jamshidi J., Azargashb E., Samangouee S. Association between vitamin D receptor gene BsmI polymorphism and bone mineral density in a population of 146 Iranian women. Cell Journal, 2013, vol. 15, no. 1, pp. 75–82.
14. Chen Chen H.-Y., Chen W.-C., Chen W.-C., Tsai F.-J., Li C.-W., Tsai C.-H. Relation of BsmI vitamin D receptor gene polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal Chinese women in Taiwan. Osteoporosis International, 2001, vol. 12, no. 12, pp. 1036–1041. https://doi.org/10.1007/s001980170014
15. Mailyan E. A. The effect of polymorphism 283 A>G (BSMI) of the vitamin D receptor gene on the development of osteoporosis in postmenopausal women. Meditsinskii vestnik Yuga Rossii [Medical Herald of the South of Russia], 2016, no. 4, pp. 32–38 (in Russian).
16. Marozik P., Mosse I., Alekna V., Rudenko E., Tamulaitienė M., Ramanau H. [et al.]. Association between polymorphisms of VDR, COL1A1, and LCT genes and bone mineral density in Belarusian women with severe postmenopausal osteoporosis. Medicina (Kaunas), 2013, vol. 49, no. 4, pp. 177–184.
17. Fu Jia, Rui-Fen Sun, Qun-Hui Li, Da-Xing Wang, Feng Zhao, Jun-Min Li [et al.]. Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genetic Testing and Molecular Biomarkers, 2012, vol. 17, no. 1, pp. 30–34. https://doi.org/10.1089/gtmb.2012.0267
18. Reference SNP (rs) Report: rs7975232. National Center for Biotechnology Information. Available at: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=7975232 (accessed 07.04.2019).
19. Houston L. A., Grant S. F., Reid D. M., Ralston S. H. Vitamin D receptor polymorphism, bone mineral density, and osteoporotic vertebral fracture: studies in a UK population. Bone, 1996, vol. 18, no. 3, pp. 249–252. https://doi.org/10.1016/8756-3282(95)00483-1
20. Fontova Garrofé R., Gutiérrez Fornés C., Broch Montané M., Aguilar Crespillo C., Pujol del Pozo A., Vendrell Ortega J. [et al.]. Polymorphism of the gene for vitamin D receptor, bone mass, and bone turnover in women with postmenopausal osteoporosis. Revista Clínica Española, 2000, vol. 200, no. 4, pp. 198–202. https://doi.org/10.1016/S0014-2565(00)70605-9
21. Mencej-Bedrač S., Preželj J., Kocjan T., Teskač K., Ostanek B., Šmelcer M., Marc J. The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density. Journal of Molecular Endocrinology, 2009, vol. 42, no. 3, pp. 239–247. https://doi.org/10.1677/jme-08-0108
22. Zajicková K., Zofková I., Bahbouh R., Krepelová A. Vitamin D receptor gene polymorphisms, bone mineral density and bone turnover: FokI genotype is related to postmenopausal bone mass. Physiological Research, 2002, vol. 51, no. 5, pp. 501–509.
23. Zhang L., Yin X., Wang J., Xu D., Wang Y., Yang J. [et al.]. Associations between VDR gene polymorphisms and osteoporosis risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis. Scientifc Reports, 2018, vol. 8, no. 1, p. 981. https://doi.org/10.1038/s41598-017-18670-7
24. Arai H., Miyamoto K., Yoshida M., Yamamoto H., Taketani Y., Morita K. [et al.]. The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. Journal of Bone and Mineral Research, 2001, vol. 16, no. 7, pp. 1256–1264. https://doi.org/10.1359/jbmr.2001.16.7.1256
25. Reference SNP (rs) Report: rs11568820. National Center for Biotechnology Information. Available at: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=11568820 (accessed 07.04.2019).
26. Shen H., Xie J., Lu H. Vitamin D receptor gene and risk of fracture in postmenopausal women: a meta-analysis. Climacteric, 2014, vol. 17, no. 4, pp. 319–324. https://doi.org/10.3109/13697137.2013.856401
27. Fang Y., Rivadeneira F., van Meurs J. B. J., Pols H. A. P., Ioannidis J. P. A., Uitterlinden A. G. Vitamin D receptor gene BsmI and TaqI polymorphisms and fracture risk: a meta-analysis. Bone, 2006, vol. 39, no. 4, pp. 938–945. https://doi.org/10.1016/j.bone.2006.04.016
Review
For citations:
Rudenka A.V., Rudenka E.V., Samokhovec V.Yu., Kobets K.V., Marozik P.M. Association of vitamin D receptor gene polymorphism with a bone mineral density level in postmenopausal women. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2019;16(2):192-201. (In Russ.) https://doi.org/10.29235/1814-6023-2019-16-2-192-201
Views: 930
Email this article 