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Association analyses of osteoprotegerin gene polymorphisms with bone mineral density in Chinese postmenopausal women

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Abstract

Osteoprotegerin gene (OPG) is an important candidate gene of osteoporosis. The objective of this study was to evaluate the association between OPG gene polymorphisms and bone mineral density (BMD). A total of 336 Chinese postmenopausal women were included in this study. OPG gene polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP), created restriction site–PCR (CRS–PCR) and DNA sequencing methods. BMD was evaluated at the lumbar spine (L2–4), total hip and femoral neck. Two single-nucleotide polymorphisms (SNPs) (g.21775C>T and g.23367T>C) were identified and the association analysis showed significant difference of spine BMD among different g.23367T>C genotype, subjects with the genotype TT was significantly higher than those of genotype TC and CC. Such a significant difference was not observed at the neck hip BMD and total hip BMD. The g.21775C>T polymorphism was not significantly associated with spine BMD, total hip BMD and neck hip BMD in the studied subjects. These findings suggested that OPG gene polymorphisms were associated with BMD in Chinese postmenopausal women. Results from this study will be helpful in further studies to determine the role of OPG gene in osteoporosis.

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References

  1. Cummings SR, Kelsey JL, Nevitt MC, O’Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev. 1985;7:178–208.

    PubMed  CAS  Google Scholar 

  2. Riggs BL, Melton LJ III. Involutional osteoporosis. N Engl J Med. 1986;314:1676–86.

    Article  PubMed  CAS  Google Scholar 

  3. Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137–41.

    Article  PubMed  CAS  Google Scholar 

  4. 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. J Genet Genomics. 2007;34:868–76.

    Article  PubMed  CAS  Google Scholar 

  5. Peck WA. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993;94:646–50.

    Google Scholar 

  6. Garcia-Unzueta MT, Riancho JA, Zarrabeitia MT, Sanudo C, Berja A, Valero C, Pesquera C, Paule B, Gonzalez-Macias J, Amado JA. Association of the 163A/G and 1181G/C osteoprotegerin polymorphism with bone mineral density. Horm Metab Res. 2008;40:219–24.

    Article  PubMed  CAS  Google Scholar 

  7. Nguyen TV, Blangero J, Eisman JA. Genetic epidemiological approaches to the search for osteoporosis genes. J Bone Miner Res. 2000;15:392–401.

    Article  PubMed  CAS  Google Scholar 

  8. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep. 2010;37:227–34.

    Article  PubMed  CAS  Google Scholar 

  9. Albagha OM, Ralston SH. Genetics and osteoporosis. Rheum Dis Clin N Am. 2006;32:659–80.

    Article  Google Scholar 

  10. Hosoi T. Genetic aspects of osteoporosis. J Bone Miner Metab. 2010;28:601–7.

    Article  PubMed  CAS  Google Scholar 

  11. Ralston SH. Genetics of osteoporosis. Ann N Y Acad Sci. 2010;1192:181–9.

    Article  PubMed  CAS  Google Scholar 

  12. Ferrari S. Human genetics of osteoporosis. Best Pract Res Clin Endocrinol Metab. 2008;22:723–35.

    Article  PubMed  CAS  Google Scholar 

  13. Cheung CL, Xiao SM, Kung AW. Genetic epidemiology of age-related osteoporosis and its clinical applications. Nat Rev Rheumatol. 2010;6:507–17.

    Article  PubMed  Google Scholar 

  14. Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S. Genetic determinants of bone mass in adults. A twin study. J Clin Invest. 1987;80:706–10.

    Article  PubMed  CAS  Google Scholar 

  15. Langdahl BL, Carstens M, Stenkjaer L, Eriksen EF. Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res. 2002;17:1245–55.

    Article  PubMed  CAS  Google Scholar 

  16. Arko B, Prezelj J, Kocijancic A, Komel R, Marc J. Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women. Maturitas. 2005;51:270–9.

    Article  PubMed  CAS  Google Scholar 

  17. Yamada Y, Ando F, Niino N, Shimokata H. Association of polymorphisms of the osteoprotegerin gene with bone mineral density in Japanese women but not men. Mol Genet Metab. 2003;80:344–9.

    Article  PubMed  CAS  Google Scholar 

  18. Vidal C, Formosa R, Xuereb-Anastasi A. Functional polymorphisms within the TNFRSF11B (osteoprotegerin) gene increase the risk for low bone mineral density. J Mol Endocrinol. 2011;47:327–33.

    Article  PubMed  CAS  Google Scholar 

  19. Arko B, Prezelj J, Komel R, Kocijancic A, Hudler P, Marc J. Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab. 2002;87:4080–4.

    Article  PubMed  CAS  Google Scholar 

  20. Hofbauer LC, Schoppet M. Osteoprotegerin gene polymorphism and the risk of osteoporosis and vascular disease. J Clin Endocrinol Metab. 2002;87:4078–9.

    Article  PubMed  CAS  Google Scholar 

  21. Fang Y, van Meurs JB, d’Alesio A, Jhamai M, Zhao H, Rivadeneira F, Hofman A, van Leeuwen JP, Jehan F, Pols HA, Uitterlinden AG. Promoter and 3′-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am J Hum Genet. 2005;77:807–23.

    Article  PubMed  CAS  Google Scholar 

  22. Li Y, Xi B, Li K, Wang C. Association between vitamin D receptor gene polymorphisms and bone mineral density in Chinese women. Mol Biol Rep. 2012;39:5709–17.

    Article  PubMed  CAS  Google Scholar 

  23. Mann V, Ralston SH. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone. 2003;32:711–7.

    Article  PubMed  CAS  Google Scholar 

  24. Yamada Y. Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis. Pharmacogenetics. 2001;11:765–71.

    Article  PubMed  CAS  Google Scholar 

  25. Ohmori H, Makita Y, Funamizu M, Hirooka K, Hosoi T, Orimo H, Suzuki T, Ikari K, Nakajima T, Inoue I, Hata A. Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis. J Hum Genet. 2002;47:400–6.

    Article  PubMed  CAS  Google Scholar 

  26. Zhao HY, Liu JM, Ning G, Zhao YJ, Zhang LZ, Sun LH, Xu MY, Uitterlinden AG, Chen JL. The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women. Osteoporos Int. 2005;16:1519–24.

    Article  PubMed  CAS  Google Scholar 

  27. Moffett SP, Oakley JI, Cauley JA, Lui LY, Ensrud KE, Taylor BC, Hillier TA, Hochberg MC, Li J, Cayabyab S, Lee JM, Peltz G, Cummings SR, Zmuda JM. Osteoprotegerin Lys3Asn polymorphism and the risk of fracture in older women. J Clin Endocrinol Metab. 2008;93:2002–8.

    Article  PubMed  CAS  Google Scholar 

  28. Kim JG, Kim JH, Kim JY, Ku SY, Jee BC, Suh CS, Kim SH, Choi YM. Association between osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women. Menopause. 2007;14:913–8.

    Article  PubMed  Google Scholar 

  29. Ueland T, Bollerslev J, Wilson SG, Dick IM, Islam FM, Mullin BH, Devine A, Prince RL. No associations between OPG gene polymorphisms or serum levels and measures of osteoporosis in elderly Australian women. Bone. 2007;40:175–81.

    Article  PubMed  CAS  Google Scholar 

  30. Jorgensen HL, Kusk P, Madsen B, Fenger M, Lauritzen JB. Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios. J Bone Miner Metab. 2004;22:132–8.

    Article  PubMed  CAS  Google Scholar 

  31. Haliassos A, Chomel JC, Tesson L, Baudis M, Kruh J, Kaplan JC, Kitzis A. Modification of enzymatically amplified DNA for the detection of point mutations. Nucleic Acids Res. 1989;17:3606.

    Article  PubMed  CAS  Google Scholar 

  32. Yuan ZR, Li J, Zhang LP, Gao X, Gao HJ, Xu SZ. Investigation on BRCA1 SNPs and its effects on mastitis in Chinese commercial cattle. Gene. 2012;505:190–4.

    Article  PubMed  CAS  Google Scholar 

  33. Yuan ZR, Chu GY, Dan Y, Li J, Zhang LP, Gao X, Gao HJ, Li JY, Xu SZ, Liu ZH. BRCA1: a new candidate gene for bovine mastitis and its association analysis between single nucleotide polymorphisms and milk somatic cell score. Mol Biol Rep. 2012;39:6625–31.

    Article  PubMed  CAS  Google Scholar 

  34. Yuan ZR, Li JY, Li J, Gao X, Xu SZ. Effects of DGAT1 gene on meat and carcass fatness quality in Chinese commercial cattle. Mol Biol Rep. 2013;40:1947–54.

    Google Scholar 

  35. Yuan ZR, Li J, Li JY, Gao X, Xu SZ. SNPs identification and its correlation analysis with milk somatic cell score in bovine MBL1 gene. Mol Biol Rep. 2013;40:7–12.

    Article  PubMed  CAS  Google Scholar 

  36. Nott A, Meislin SH, Moore MJ. A quantitative analysis of intron effects on mammalian gene expression. RNA. 2003;9:607–17.

    Article  PubMed  CAS  Google Scholar 

  37. Zheng X, Ju Z, Wang J, Li Q, Huang J, Zhang A, Zhong J, Wang C. Single nucleotide polymorphisms, haplotypes and combined genotypes of LAP3 gene in bovine and their association with milk production traits. Mol Biol Rep. 2011;38:4053–61.

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Orthopedics Department, The Second Affiliated Hospital Zhejiang University College of Medicine, No. 88 Jiefang Road, Hangzhou, 310009, People’s Republic of China

    Feng Zhang, Chunlei He, Gang Chen, Fangcai Li & Hui Gao

  2. Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, No. 23, Qingnian Road, Ganzhou, 341000, Jiangxi Province, People’s Republic of China

    Hui Gao

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  1. Feng Zhang
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  2. Chunlei He
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  3. Gang Chen
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  4. Fangcai Li
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Correspondence to Hui Gao.

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Feng Zhang and Chunlei He contributed equally to this paper.

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Zhang, F., He, C., Chen, G. et al. Association analyses of osteoprotegerin gene polymorphisms with bone mineral density in Chinese postmenopausal women. Med Oncol 30, 389 (2013). https://doi.org/10.1007/s12032-012-0389-3

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  • DOI: https://doi.org/10.1007/s12032-012-0389-3

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