Rheumatology International

, Volume 29, Issue 5, pp 539–544 | Cite as

Association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density: a meta-analysis

  • Young Ho Lee
  • Jin-Hyun Woo
  • Seong Jae Choi
  • Jong Dae Ji
  • Gwan Gyu Song
Original Article

Abstract

The association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density (BMD) has been studied, but results have been mixed. Accordingly, the authors performed a meta-analysis on studies on the association between the A1330V LRP5 polymorphism and BMD. Appropriate studies were identified using MEDLINE and by manual searching. A total of 7 separate comparisons were considered in this meta-analysis. Individuals with the AA genotype showed significantly higher lumbar BMD than those with the AV/VV or VV genotype. Weighted mean differences (WMDs) were 0.147 g/cm2 (95% confidence interval [CI] 0.069–0.224, P < 0.001) and 0.182 g/cm2 (95% CI 0.024–0.340, P = 0.024) without between-study heterogeneity for AA versus AV/VV and AA versus VV, respectively. Six studies analyzed femur neck (FN) BMD. Individuals with the AA genotype had a significantly higher FN BMD than those with the AV/VV genotype (WMD = 0.165 g/cm2, 95% CI = 0.087–0.215, P < 0.001), without between-study heterogeneity. Trochanter BMD was measured in three studies. Results showed that subjects with the AA genotype tended to have higher BMD than patients with the AV or VV genotype (WMD = 0.136 g/cm2, 95% CI = −0.002 to 0.274, P = 0.053). In conclusion, this meta-analysis shows that the LRP5 A1330V polymorphism is associated with BMD, and that individuals with the AA genotype have a higher BMD than those with the AV/VV or VV genotype.

Keywords

LRP5 Polymorphism Bone mineral density Meta-analysis 

References

  1. 1.
    Nguyen TV, Blangero J, Eisman JA (2000) Genetic epidemiological approaches to the search for osteoporosis genes. J Bone Miner Res 15:392–401. doi:10.1359/jbmr.2000.15.3.392 PubMedCrossRefGoogle Scholar
  2. 2.
    Zmuda JM, Cauley JA, Ferrell RE (1999) Recent progress in understanding the genetic susceptibility to osteoporosis. Genet Epidemiol 16:356–367. doi:10.1002/(SICI)1098-2272(1999)16:4<356::AID-GEPI3>3.0.CO;2-IPubMedCrossRefGoogle Scholar
  3. 3.
    Johnson ML, Harnish K, Nusse R, Van Hul W (2004) LRP5 and Wnt signaling: a union made for bone. J Bone Miner Res 19:1749–1757. doi:10.1359/JBMR.040816 PubMedCrossRefGoogle Scholar
  4. 4.
    Wodarz A, Nusse R (1998) Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol 14:59–88. doi:10.1146/annurev.cellbio.14.1.59 PubMedCrossRefGoogle Scholar
  5. 5.
    Koller DL, Rodriguez LA, Christian JC, Slemenda CW, Econs MJ, Hui SL, Morin P, Conneally PM, Joslyn G, Curran ME, Peacock M, Johnston CC, Foroud T (1998) Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12–13. J Bone Miner Res 13:1903–1908. doi:10.1359/jbmr.1998.13.12.1903 PubMedCrossRefGoogle Scholar
  6. 6.
    Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523. doi:10.1016/S0092-8674(01)00571-2 PubMedCrossRefGoogle Scholar
  7. 7.
    Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521. doi:10.1056/NEJMoa013444 PubMedCrossRefGoogle Scholar
  8. 8.
    Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L (2002) Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 157:303–314. doi:10.1083/jcb.200201089 PubMedCrossRefGoogle Scholar
  9. 9.
    Giroux S, Elfassihi L, Cardinal G, Laflamme N, Rousseau F (2007) LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women. Bone 40:1299–1307. doi:10.1016/j.bone.2007.01.004 PubMedCrossRefGoogle Scholar
  10. 10.
    Ezura Y, Nakajima T, Urano T, Sudo Y, Kajita M, Yoshida H, Suzuki T, Hosoi T, Inoue S, Shiraki M, Emi M (2007) Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. Bone 40:997–1005. doi:10.1016/j.bone.2005.06.025 PubMedCrossRefGoogle Scholar
  11. 11.
    Saarinen A, Valimaki VV, Valimaki MJ, Loyttyniemi E, Auro K, Uusen P, Kuris M, Lehesjoki AE, Makitie O (2007) The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men. Bone 40:1006–1012. doi:10.1016/j.bone.2006.11.010 PubMedCrossRefGoogle Scholar
  12. 12.
    van Meurs JB, Rivadeneira F, Jhamai M, Hugens W, Hofman A, van Leeuwen JP, Pols HA, Uitterlinden AG (2006) Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. J Bone Miner Res 21:141–150. doi:10.1359/JBMR.050904 PubMedCrossRefGoogle Scholar
  13. 13.
    Zhang ZL, Qin YJ, He JW, Huang QR, Li M, Hu YQ, Liu YJ (2005) Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women. Acta Pharmacol Sin 26:1111–1116. doi:10.1111/j.1745-7254.2005.00173.x PubMedCrossRefGoogle Scholar
  14. 14.
    Koh JM, Jung MH, Hong JS, Park HJ, Chang JS, Shin HD, Kim SY, Kim GS (2004) Association between bone mineral density and LDL receptor-related protein 5 gene polymorphisms in young Korean men. J Korean Med Sci 19:407–412PubMedCrossRefGoogle Scholar
  15. 15.
    Koay MA, Woon PY, Zhang Y, Miles LJ, Duncan EL, Ralston SH, Compston JE, Cooper C, Keen R, Langdahl BL, MacLelland A, O’Riordan J, Pols HA, Reid DM, Uitterlinden AG, Wass JA, Brown MA (2004) Influence of LRP5 polymorphisms on normal variation in BMD. J Bone Miner Res 19:1619–1627. doi:10.1359/JBMR.040704 PubMedCrossRefGoogle Scholar
  16. 16.
    Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Benichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W (2003) Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet 72:763–771. doi:10.1086/368277 PubMedCrossRefGoogle Scholar
  17. 17.
    Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315:1533–1537PubMedGoogle Scholar
  18. 18.
    Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedGoogle Scholar
  19. 19.
    Davey SG, Egger M (1997) Meta-analyses of randomised controlled trials. Lancet 350:1182Google Scholar
  20. 20.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. doi:10.1002/sim.1186 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Young Ho Lee
    • 1
  • Jin-Hyun Woo
    • 1
  • Seong Jae Choi
    • 1
  • Jong Dae Ji
    • 1
  • Gwan Gyu Song
    • 1
  1. 1.Division of Rheumatology, Department of Internal MedicineKorea University Medical CenterSeoulSouth Korea

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