Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women

详细信息    查看全文

• 作者：P. Tu ; P. Duan ; R.-S. Zhang ; D.-B. Xu ; Y. Wang ; H.-P. Wu…
• 关键词：BMD ; OPG ; Post ; menopause ; RANK ; RANKL
• 刊名：Osteoporosis International
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：26
• 期：1
• 页码：179-185
• 全文大小：319 KB
• 参考文献：1. Lane NE (2006) Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol (2 Suppl):S3-11
  2. Li WF, Hou SX, Yu B, Li MM, Ferec C, Chen JM (2010) Genetics of osteoporosis: accelerating pace in gene identification and validation. Hum Genet 3:249-85 CrossRef
  3. Slemenda CW, Turner CH, Peacock M, Christian JC, Sorbel J, Hui SL, Johnston CC (1996) The genetics of proximal femur geometry, distribution of bone mass and bone mineral density. Osteoporos Int 2:178-82 CrossRef
  4. Smith DM, Nance WE, Kang KW, Christian JC, Johnston CC Jr (1973) Genetic factors in determining bone mass. J Clin Invest 11:2800-808 CrossRef
  5. Arden NK, Baker J, Hogg C, Baan K, Spector TD (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. J Bone Miner Res 4:530-34
  6. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 3:337-49
  7. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 6937:337-42 CrossRef
  8. Liu C, Walter TS, Huang P, Zhang S, Zhu X, Wu Y, Wedderburn LR, Tang P, Owens RJ, Stuart DI, Ren J, Gao B (2010) Structural and functional insights of RANKL-RANK interaction and signaling. J Immunol 12:6910-919 CrossRef
  9. Boyce BF, Xing L (2007) Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther Suppl 1:S1 CrossRef
  10. Richards JB, Zheng HF, Spector TD (2012) Genetics of osteoporosis from genome-wide association studies: advances and challenges. Nat Rev Genet 8:576-88 CrossRef
  11. Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD (2008) Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 9623:1505-512 CrossRef
  12. Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Richards JB et al (2009) Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet 41(11):1199-206 CrossRef
  13. Richards JB, Kavvoura FK, Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Zillikens MC, Wilson SG, Mullin BH, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra BA, Pols HA, Sigurdsson G, Thorsteinsdottir U, Soranzo N, Williams FM, Zhou Y, Ralston SH, Thorleifsson G, van Duijn CM, Kiel DP, Stefansson K, Uitterlinden AG, Ioannidis JP, Spector TD, Genetic Factors for Osteoporosis Consortium (2009) Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med 8:528-37 CrossRef
  14. Zheng HF, Tobias JH, Duncan E, Evans DM, Eriksson J, Paternoster L, Yerges-Armstrong LM, Lehtim?ki T, Bergstr?m U, K?h?nen M, Leo PJ, Raitakari O, Laaksonen M, Nicholson GC, Viikari J, Ladouceur M, Lyytik?inen LP, Medina-Gomez C, Rivadeneira F, Prince RL, Sievanen H, Leslie WD, Mellstr?m D, Eisman JA, Movérare-Skrtic S, Goltzman D, Hanley DA, Jones G, St Pourcain B, Xiao Y, Timpson NJ, Smith GD, Reid IR, Ring SM, Sambrook PN, Karlsson M, Dennison EM, Kemp JP, Danoy P, Sayers A, Wilson SG, Nethander M, McCloskey E, Vandenput L, Eastell R, Liu J, Spector T, Mitchell BD, Streeten EA, Brommage R, Pettersson-Kymmer U, Brown MA, Ohlsson C, Richards JB, Lorentzon M (2012) WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Ge
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Orthopedics
  Gynecology
  Endocrinology
  Rheumatology
  
• 出版者：Springer London
• ISSN：1433-2965

文摘

Summary Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. Introduction The aim of this study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in a cohort of Chinese post-menopausal women. Methods A cross-sectional study was conducted in 881 post-menopausal women aged 50-9?years. All participants underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were genotyped. We tested whether a single SNP or a haplotype was associated with BMD variations. Results Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and one in the TNFRSF11A gene (rs7239261) were found to be significantly associated with FN BMD (p--.014, 0.013, and 0.047, respectively). Haplotype TGACGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic risk factor toward a lower FN BMD (beta-??0.1473; p--.01126). In contrary, haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was genetic protective factor for LS BMD (beta--.3923; p--.04917). Conclusions Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health.