The influence of vitamin D receptor genetic variants on bone mineral density and osteoporosis in Chinese postmenopausal women

Wei He, Ming Liu, Xiaonan Huang, Zuhong Qing, Wei Gao, Wei He, Ming Liu, Xiaonan Huang, Zuhong Qing, Wei Gao

Abstract

Growing evidence indicates that the vitamin D receptor (VDR) gene is an important candidate gene for influencing the development of osteoporosis. The aim of the study was to evaluate the potential association between genetic variants of VDR gene and bone mineral density (BMD) and osteoporosis in Chinese postmenopausal women. The study included 970 Chinese postmenopausal women at the postmenopausal osteoporosis (482) and healthy controls (488). The BMD of lumbar spine (L(2-4) anterior-posterior view), femoral neck hip, and total hip was evaluated using the Norland XR-46 dual energy X-ray absorptiometry (DEXA). The genotypes of VDR genetic variants were determined by the created restriction site-PCR (CRS-PCR) and confirmed by DNA sequencing methods. Our data indicated that the VDR p.Glicine (Gly)14 alanine (Ala) and p.histidine (His) 305 glutanine (Gln) genetic variants were statistically associated with adjusted femoral neck hip BMD, adjusted lumbar spine BMD, and adjusted total hip BMD (P values < 0.05). Results from this study suggest that the VDR p.Gly14Ala and p.His305Gln genetic variants are significantly associated with BMD decrease in Chinese postmenopausal women and might be used as molecular markers for assessing the risk of BMD and osteoporosis.

References

    1. Cummings S. R., Kelsey J. L., Nevitt M. C., O'Dowd K. J. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiologic Reviews. 1985;7:178–208.
    1. Riggs B. L., Melton L. J., III Involutional osteoporosis. The New England Journal of Medicine. 1986;314(26):1676–1686. doi: 10.1056/nejm198606263142605.
    1. Kanis J. A., Melton L. J., III, Christiansen C., Johnston C. C., Khaltaev N. The diagnosis of osteoporosis. Journal of Bone and Mineral Research. 1994;9(8):1137–1141.
    1. Geng L., Yao Z., Yang H., Luo J., Han L., Lu Q. Association of CA repeat polymorphism in estrogen receptor beta gene with postmenopausal osteoporosis in Chinese. Journal of Genetics and Genomics. 2007;34(10):868–876. doi: 10.1016/s1673-8527(07)60098-8.
    1. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. The American Journal of Medicine. 1993;94(6):646–650. doi: 10.1016/0002-9343(93)90218-e.
    1. García-Unzueta M. T., Riancho J. A., Zarrabeitia M. T., et al. Association of the 163A/G and 1181G/C osteoprotegerin polymorphism with bone mineral density. Hormone and Metabolic Research. 2008;40(3):219–224. doi: 10.1055/s-2008-1046793.
    1. Lee Y. H., Woo J.-H., Choi S. J., Ji J. D., Song G. G. Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Molecular Biology Reports. 2010;37(1):227–234. doi: 10.1007/s11033-009-9637-9.
    1. Li Y., Xi B., Li K., Wang C. Association between vitamin D receptor gene polymorphismsand bone mineral density in Chinese women. Molecular Biology Reports. 2012;39(5):5709–5717. doi: 10.1007/s11033-011-1380-3.
    1. Mohammadi Z., Fayyazbakhsh F., Ebrahimi M., et al. Association between vitamin D receptor gene polymorphisms (Fok1 and Bsm1) and osteoporosis: a systematic review. Journal of Diabetes & Metabolic Disorders. 2014;13, article 98 doi: 10.1186/s40200-014-0098-x.
    1. Kanan R. M. The effect of FokI vitamin D receptor polymorphism on bone mineral density in Jordanian perimenopausal women. Indian Journal of Human Genetics. 2013;19(2):233–238. doi: 10.4103/0971-6866.116125.
    1. Wang D., Liu R., Zhu H., Zhou D., Mei Q., Xu G. Vitamin D receptor Fok I polymorphism is associated with low bone mineral density in postmenopausal women: a meta-analysis focused on populations in Asian countries. European Journal of Obstetrics Gynecology and Reproductive Biology. 2013;169(2):380–386. doi: 10.1016/j.ejogrb.2013.03.031.
    1. Morrison N. A., Yeoman R., Kelly P. J., Eisman J. A. Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphisms and circulating osteocalcin. Proceedings of the National Academy of Sciences of the United States of America. 1992;89(15):6665–6669. doi: 10.1073/pnas.89.15.6665.
    1. Morrison N. A., Qi J. C., Tokita A., et al. Prediction of bone density from vitamin D receptor alleles. Nature. 1994;367:284–287.
    1. Fang Y., van Meurs J. B. J., D'Alesio A., et al. Promoter and 3′-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the Rotterdam Study. The American Journal of Human Genetics. 2005;77(5):807–823. doi: 10.1086/497438.
    1. Kurt O., Yilmaz-Aydogan H., Uyar M., Isbir T., Seyhan M. F., Can A. Evaluation of ERalpha and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women. Molecular Biology Reports. 2012;39(6):6723–6730. doi: 10.1007/s11033-012-1496-0.
    1. Jakubowska-Pietkiewicz E., Młynarski W., Klich I., Fendler W., Chlebna-Sokół D. Vitamin D receptor gene variability as a factor influencing bone mineral density in pediatric patients. Molecular Biology Reports. 2012;39(5):6243–6250. doi: 10.1007/s11033-012-1444-z.
    1. Horst-Sikorska W., Dytfeld J., Wawrzyniak A., et al. Vitamin D receptor gene polymorphisms, bone mineral density and fractures in postmenopausal women with osteoporosis. Molecular Biology Reports. 2013;40(1):383–390. doi: 10.1007/s11033-012-2072-3.
    1. Hussien Y. M., Shehata A., Karam R. A., Alzahrani S. S., Magdy H., El-Shafey A. M. Polymorphism in vitamin D receptor and osteoprotegerin genes in Egyptian rheumatoid arthritis patients with and without osteoporosis. Molecular Biology Reports. 2013;40(5):3675–3680. doi: 10.1007/s11033-012-2443-9.
    1. Garnero P., Borel O., Sornay-Rendu E., Delmas P. D. Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women. Journal of Bone and Mineral Research. 1995;10(9):1283–1288.
    1. Fleet J. C., Harris S. S., Wood R. J., Dawson-Hughes B. The BsmI vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women. Journal of Bone and Mineral Research. 1995;10(6):985–990.
    1. Morita A., Iki M., Dohi Y., et al. Prediction of bone mineral density from vitamin D receptor polymorphisms is uncertain in representative samples of Japanese Women. The Japanese Population-based Osteoporosis (JPOS) Study. International Journal of Epidemiology. 2004;33(5):979–988. doi: 10.1093/ije/dyh245.
    1. Eccleshall T. R., Garnero P., Gross C., Delmas P. D., Feldman D. Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal french women: the OFELY Study. Journal of Bone and Mineral Research. 1998;13(1):31–35. doi: 10.1359/jbmr.1998.13.1.31.
    1. Vandevyver C., Wylin T., Cassiman J.-J., Raus J., Geusens P. Influence of the vitamin D receptor gene alleles on bone mineral density in postmenopausal and osteoporotic women. Journal of Bone and Mineral Research. 1997;12(2):241–247. doi: 10.1359/jbmr.1997.12.2.241.
    1. Qin G., Dong Z., Zeng P., Liu M., Liao X. Association of vitamin D receptor BsmI gene polymorphism with risk of osteoporosis: a meta-analysis of 41 studies. Molecular Biology Reports. 2013;40(1):497–506. doi: 10.1007/s11033-012-2086-x.
    1. Singh M., Singh P., Singh S., Juneja P. K., Kaur T. Vitamin D receptor (VDR) gene polymorphism influences the risk of osteoporosis in postmenopausal women of Northwest India. Archives of osteoporosis. 2013;8(1-2):p. 147. doi: 10.1007/s11657-013-0147-y.
    1. Rojano-Mejía D., Coral-Vázquez R. M., Coronel A., et al. Relation of the estrogen receptor and vitamin D receptor polymorphisms with bone mineral density in postmenopausal Mexican-mestizo women. Gene. 2014;537(1):10–14. doi: 10.1016/j.gene.2013.12.054.
    1. 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;15(1):75–82.
    1. Marozik P., Mosse I., Alekna V., 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;49(4):177–184.
    1. Jia F., Sun R. F., Li Q. H., et al. Vitamin D receptor bsmi polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genetic Testing and Molecular Biomarkers. 2013;17(1):30–34. doi: 10.1089/gtmb.2012.0267.
    1. González-Mercado A., Sánchez-López J. Y., Regla-Nava J. A., et al. Association analysis of vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Mexican-Mestizo women. Genetics and Molecular Research. 2013;12(3):2755–2763. doi: 10.4238/2013.July.30.13.
    1. Casado-Díaz A., Cuenca-Acevedo R., Navarro-Valverde C., et al. Vitamin D status and the Cdx-2 polymorphism of the vitamin D receptor gene are determining factors of bone mineral density in young healthy postmenopausal women. Journal of Steroid Biochemistry and Molecular Biology. 2013;136(1):187–189. doi: 10.1016/j.jsbmb.2012.09.026.
    1. Canto-Cetina T., Cetina Manzanilla J. A., González Herrera L., et al. VDR polymorphisms are associated with bone mineral density in post-menopausal Mayan-Mestizo women. Annals of Human Biology. 2014 doi: 10.3109/03014460.2014.967295.
    1. Ohmori H., Makita Y., Funamizu M., et al. Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis. Journal of Human Genetics. 2002;47(8):400–406. doi: 10.1007/s100380200058.
    1. Albagha O. M. E., Ralston S. H. Genetics and osteoporosis. Rheumatic Disease Clinics of North America. 2006;32(4):659–680.
    1. Hosoi T. Genetic aspects of osteoporosis. Journal of Bone and Mineral Metabolism. 2010;28(6):601–607. doi: 10.1007/s00774-010-0217-9.
    1. Ralston S. H. Genetics of osteoporosis. Annals of the New York Academy of Sciences. 2010;1192:181–189. doi: 10.1111/j.1749-6632.2009.05317.x.
    1. Ferrari S. Human genetics of osteoporosis. Best Practice & Research Clinical Endocrinology & Metabolism. 2008;22:723–735.
    1. Cheung C.-L., Xiao S.-M., Kung A. W. C. Genetic epidemiology of age-related osteoporosis and its clinical applications. Nature Reviews Rheumatology. 2010;6(9):507–517. doi: 10.1038/nrrheum.2010.106.
    1. Zhao H. Y., Liu J. M., Ning G., et al. The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women. Osteoporosis International. 2005;16(12):1519–1524. doi: 10.1007/s00198-005-1865-9.
    1. Zmuda J. M., Cauley J. A., Ferrell R. E. Molecular epidemiology of vitamin D receptor gene variants. Epidemiologic Reviews. 2000;22(2):203–217. doi: 10.1093/oxfordjournals.epirev.a018033.
    1. Moore D. D., Kato S., Xie W., et al. International union of pharmacology. LXII. The NR1H and NR1I receptors: Constitutive androstane receptor, pregnene X receptor, farnesoid X receptor α, farnesoid X receptor β, liver X receptor α, liver X receptor β, and vitamin D receptor. Pharmacological Reviews. 2006;58(4):742–759. doi: 10.1124/pr.58.4.6.
    1. Ferrari S., Bonjour J.-P., Rizzoli R. The vitamin D receptor gene and calcium metabolism. Trends in Endocrinology and Metabolism. 1998;9(7):259–265. doi: 10.1016/S1043-2760(98)00065-4.
    1. Tothill P., Laskey M. A., Orphanidou C. I., van Wijk M. Anomalies in dual energy X-ray absorptiometry measurements of total-body bone mineral during weight change using Lunar, Hologic and Norland instruments. British Journal of Radiology. 1999;72:661–669. doi: 10.1259/bjr.72.859.10624323.
    1. Haliassos A., Chomel J. C., Tesson L., et al. Modification of enzymatically amplified DNA for the detection of point mutations. Nucleic Acids Research. 1989;17(9, article 3606) doi: 10.1093/nar/17.9.3606.
    1. Yuan Z., Li J., Gao X., Xu S. SNPs identification and its correlation analysis with milk somatic cell score in bovine MBL1 gene. Molecular Biology Reports. 2013;40(1):7–12. doi: 10.1007/s11033-012-1934-z.
    1. Yuan Z., Li J., Li J., et al. Investigation on BRCA1 SNPs and its effects on mastitis in Chinese commercial cattle. Gene. 2012;505(1):190–194. doi: 10.1016/j.gene.2012.05.010.
    1. Yuan Z., Li J., Gao X., Gao H., Xu S. Effects of DGAT1 gene on meat and carcass fatness quality in Chinese commercial cattle. Molecular Biology Reports. 2013;40(2):1947–1954. doi: 10.1007/s11033-012-2251-2.
    1. Zhao C. J., Li N., Deng X. M. The establishment of method for identifying SNP genotype by CRS-PCR. Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji. 2003;25:327–329.
    1. Weinstein R. S., Jilka R. L., Michael Parfitt A., Manolagas S. C. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts end osteocytes by glucocorticoids potential mechanisms of their deleterious effects on bone. Journal of Clinical Investigation. 1998;102(2):274–282. doi: 10.1172/jci2799.

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