Association between the vitamin D receptor gene polymorphism and osteoporosis

Wu,Ju; Shang,De‑Peng; Yang,Sheng; Fu,Da‑Peng; Ling,Hao‑Yi; Hou,Shuang‑Shuang; Lu,Jian‑Min

doi:10.3892/br.2016.697

Association between the vitamin D receptor gene polymorphism and osteoporosis

Authors:
- Ju Wu
- De‑Peng Shang
- Sheng Yang
- Da‑Peng Fu
- Hao‑Yi Ling
- Shuang‑Shuang Hou
- Jian‑Min Lu
View Affiliations

Affiliations: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China
Published online on: May 31, 2016 https://doi.org/10.3892/br.2016.697
Pages: 233-236

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The influence of the vitamin D receptor (VDR) gene for the risk of osteoporosis remains to be elucidated. The aim of the present study was to understand the distribution of various single‑nucleotide polymorphisms (SNPs) within the VDR gene and its association with the risk of osteoporosis. In total, 378 subjects without a genetic relationship were recruited to the study between January 2013 and July 2015. The subjects were divided into three groups, which were the normal (n=234), osteoporosis (n=65) and osteoporosis with osteoporotic fracture (n=79) groups. Three pertinent SNPs of the VDR gene rs17879735 (ApaI, Allele A/a, SNP C>A) were examined with polymerase chain reaction‑restriction fragment length polymorphism. The bone mineral density (BMD) of the lumbar spine (L2–L4), femoral neck, Ward's and Tro was measured using dual‑energy X‑ray absorptiometry. The distributions of genotype frequencies aa, AA and Aa were 48.68, 42.86 and 8.46%, separately. Following analysis of each site, BMD, body mass index (BMI) and age, BMD for each site was negatively correlated with age (P<0.01) and positively correlated with BMI (P<0.01). Correction analysis revealed that there were significant differences in the Ward's triangle BMD among each genotype (P<0.05), in which the aa genotype exhibited the lower BMD (P<0.05). No significant difference was identified among the different genotypes in the occurrence of osteoporosis with osteoporotic fracture (P>0.05). In conclusion, these indicated that the VDR gene ApaI polymorphisms had an important role in the osteoporosis risk.

View Figures

View References

1	Kelly PJ, Morrison NA, Sambrook PN, Nguyen TV and Eisman JA: Genetic influences on bone turnover, bone density and fracture. Eur J Endocrinol. 133:265–271. 1995. View Article : Google Scholar : PubMed/NCBI
2	Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN and Eberl S: Genetic determinants of bone mass in adults. A twin study. J Clin Invest. 80:706–710. 1987. View Article : Google Scholar : PubMed/NCBI
3	Guéguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J and Siest G: Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res. 10:2017–2022. 1995. View Article : Google Scholar : PubMed/NCBI
4	Yoshida T and Stern PH: How vitamin D works on bone. Endocrinol Metab Clin North Am. 41:557–569. 2012. View Article : Google Scholar : PubMed/NCBI
5	Carlberg C and Molnar F: Current status of vitamin D signaling and its therapeutic applications. Curr Top Med Chem. 12:528–547. 2012. View Article : Google Scholar : PubMed/NCBI
6	Turner AG, Anderson PH and Morris HA: Vitamin D and bone health. Scand J Clin Lab Invest Suppl. 243:65–72. 2012.PubMed/NCBI
7	Bouillon R, Okamura WH and Norman AW: Structure-function relationships in the vitamin D endocrine system. Endocr Rev. 16:200–257. 1995. View Article : Google Scholar : PubMed/NCBI
8	Miyamoto K, Kesterson RA, Yamamoto H, Taketani Y, Nishiwaki E, Tatsumi S, Inoue Y, Morita K, Takeda E and Pike JW: Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol. 11:1165–1179. 1997. View Article : Google Scholar : PubMed/NCBI
9	Taymans SE, Pack S, Pak E, Orban Z, Barsony J, Zhuang Z and Stratakis CA: The human vitamin D receptor gene (VDR) is localized to region 12cen-q12 by fluorescent in situ hybridization and radiation hybrid mapping: Genetic and physical VDR map. J Bone Miner Res. 14:1163–1166. 1999. View Article : Google Scholar : PubMed/NCBI
10	Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN and Eisman JA: Prediction of bone density from vitamin D receptor alleles. Nature. 367:284–287. 1994. View Article : Google Scholar : PubMed/NCBI
11	Sainz J, Van Tornout JM, Loro ML, Sayre J, Roe TF and Gilsanz V: Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent. N Engl J Med. 337:77–82. 1997. View Article : Google Scholar : PubMed/NCBI
12	Kurabayashi T, Tomita M, Matsushita H, Yahata T, Honda A, Takakuwa K and Tanaka K: Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women. Am J Obstet Gynecol. 180:1115–1120. 1999. View Article : Google Scholar : PubMed/NCBI
13	Mencej-Bedrac S, Prezelj J, Kocjan T, Teskac K, Ostanek B, Smelcer M and 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. J Mol Endocrinol. 42:239–247. 2009. View Article : Google Scholar : PubMed/NCBI
14	Gong G, Stern HS, Cheng SC, Fong N, Mordeson J, Deng HW and Recker RR: The association of bone mineral density with vitamin D receptor gene polymorphisms. Osteoporos Int. 9:55–64. 1999. View Article : Google Scholar : PubMed/NCBI
15	Thakkinstian A, D'Este C, Eisman J, Nguyen T and Attia J: Meta-analysis of molecular association studies: Vitamin D receptor gene polymorphisms and BMD as a case study. J Bone Miner Res. 19:419–428. 2004. View Article : Google Scholar : PubMed/NCBI
16	Thakkinstian A, D'Este C and Attia J: Haplotype analysis of VDR gene polymorphisms: A meta-analysis. Osteoporos Int. 15:729–734. 2004. View Article : Google Scholar : PubMed/NCBI
17	Li Y, Xi B, Li K and Wang C: Association between vitamin D receptor gene polymorphisms and bone mineral density in Chinese women. Mol Biol Rep. 39:5709–5717. 2012. View Article : Google Scholar : PubMed/NCBI
18	Fang Y, Rivadeneira F, van Meurs JB, Pols HA, Ioannidis JP and Uitterlinden AG: Vitamin D receptor gene BsmI and TaqI polymorphisms and fracture risk: A meta-analysis. Bone. 39:938–945. 2006. View Article : Google Scholar : PubMed/NCBI
19	Uitterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Reeve J, et al: APOSS Investigators; EPOS Investigators; EPOLOS Investigators; FAMOS Investigators; LASA Investigators; Rotterdam Study Investigators; GENOMOS Study: The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Intern Med. 145:255–264. 2006. View Article : Google Scholar : PubMed/NCBI
20	Zintzaras E, Rodopoulou P and Koukoulis GN: BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and the risk of osteoporosis: a meta-analysis. Dis Markers. 22:317–326. 2006. View Article : Google Scholar : PubMed/NCBI
21	Qin G, Dong Z, Zeng P, Liu M and Liao X: Association of vitamin D receptor BsmI gene polymorphism with risk of osteoporosis: A meta-analysis of 41 studies. Mol Biol Rep. 40:497–506. 2013. View Article : Google Scholar : PubMed/NCBI
22	WHO Europe: A Declaration on the Promotion of Patients' Rights in Europe. European Journal of Health Law. 1:279–291. 1994. View Article : Google Scholar
23	Liu CL, Wu Y and Bi LF: Progress in osteoporosis-related gene research. Zhongguoguzhishusongzazhi. 8:731–735. 2011.
24	Bustamante M, Nogués X, Enjuanes A, Elosua R, García-Giralt N, Pérez-Edo L, Cáceres E, Carreras R, Mellibovsky L, Balcells S, et al: COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women. Osteoporos Int. 18:235–243. 2007. View Article : Google Scholar : PubMed/NCBI
25	Wu D: The application of molecular genetics in osteoporosis diagnosis. Chinese Journal of Osteoporosis. 5:440–452. 2011.
26	Lu HJ, Li HL, Hao P, Li JM and Zhou LF: Association of the vitamin D receptor gene start codon polymorphism with vitamin D deficiency rickets. Zhonghua Er Ke Za Zhi. 41:493–496. 2003.(In Chinese). PubMed/NCBI
27	He JW, Huang QR, Zhang ZL, Qin YJ, Lu JH, Li M, Zhou Q, Hu YQ, Liu YJ and Zhang H: Association of polymorphisms of estrogen receptor-α and vitamin D receptor genes with peak bone mass in Shanghai women. Chinese Journal of Endocrinology and Metabolism. 20:140–142. 2004.
28	Ye W, Peng Y, Huang DS, Liu SL, Ma NF, et al: Association of the promoter −509 C>T polymorphism of transforming growth factor-β1 with lumbar disc disease. Orthopedic Journal of China. 14:531–534. 2006.
29	Lei SF, Wu Y and Deng HW: Study progress of association of the vitamin D receptor α gene with OP. zhonghualaonianyixuezazhi. 24:473–475. 2005.
30	Bell NH, Morrison NA, Nguyen TV, Eisman J and Hollis BW: ApaI polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men. J Lab Clin Med. 137:133–140. 2001. View Article : Google Scholar : PubMed/NCBI
31	Dundar U, Solak M, Kavuncu V, Ozdemir M, Cakir T, Yildiz H and Evcik D: Evidence of association of vitamin D receptor Apa I gene polymorphism with bone mineral density in postmenopausal women with osteoporosis. Clin Rheumatol. 28:1187–1191. 2009. View Article : Google Scholar : PubMed/NCBI
32	Choi YM, Jun JK, Choe J, Hwang D, Park SH, Ku SY, Kang D, Kim JG, Moon SY and Lee JY: Association of the vitamin D receptor start codon polymorphism (FokI) with bone mineral density in postmenopausal Korean women. J Hum Genet. 45:280–283. 2000. View Article : Google Scholar : PubMed/NCBI
33	Zambrano-Morales M, Borjas L, Fernández E, Zabala W, de Romero P, Pineda L and Morales-Machín A: Association of the vitamin D receptor gene BBAAtt haplotype with osteoporosis in post-menopausic women. Invest Clin. 49:29–38. 2008.(In Spanish). PubMed/NCBI
34	Quevedo LI, Martínez BM, Castillo NM and Rivera FN: Vitamin D receptor gene polymorphisms and risk of hip fracture in Chilean elderly women. Rev Med Chil. 136:475–481. 2008.(In Spanish). PubMed/NCBI
35	Boschitsch E, Suk EK, Mayr WR, Lang T, Schwartz WM and Panzer S: Genotypes of the vitamin-D-receptor gene and bone mineral density in Caucasoid postmenopausal females. Maturitas. 24:91–96. 1996. View Article : Google Scholar : PubMed/NCBI
36	Huang QR, Zhang ZL, Qin YJ, He JW, Lu JH, et al: Association of vitamin D receptor Apa polymorphism with BMD of man. Acta Acad Med Sinicae. 25:254–257. 2003.
37	Zhao J, Zhou X, Meng X, Liu G, Xing X, Liu H and Xu L: Polymorphisms of vitamin D receptor gene and its association with bone mineral density and osteocalcin in Chinese. Chin Med J (Engl). 110:366–371. 1997.PubMed/NCBI
38	Lau EM, Lam V, Li M, Ho K and Woo J: Vitamin D receptor start codon polymorphism (Fok I) and bone mineral density in Chinese men and women. Osteoporos Int. 13:218–221. 2002. View Article : Google Scholar : PubMed/NCBI