Although P2 receptor genes have been shown to be candidate genes for the development of osteoporosis, https://www.selleckchem.com/products/cb-839.html these genes were not identified by GWAS at a genome-wide significance level. Moreover, the effect sizes of SNPs are relatively small in
a polygenetic trait such as BMD. However, current GWAS studies are best powered for SNPs with a population frequency in the range of 10 to 90 %. Therefore, a relatively rare polymorphisms such as most of the non-synonymous SNPs in the P2XR7 would likely have been missed in GWAS studies. In conclusion, our results show that genetic aberration of P2X7R function is associated with BMD and osteoporosis risk in a cohort of fracture patients. Mapping P2X7R function genetically might therefore be a useful diagnostic tool for the management of osteoporosis in an early stage. Our findings warrant further observational studies GDC-0973 chemical structure in which fracture incidence as a major endpoint in relation to genetic variation in P2X7R function is prospectively monitored in addition to BMD. Acknowledgements The work was supported by the European Commission under the 7th Framework Programme, performed as the collaborative project “Fighting Osteoporosis by blocking nucleotides:
purinergic signalling in bone formation and homeostasis” (ATPBone), with participants; Copenhagen University Hospital, University College London, Maastricht University, University of Ferrara, University very of Liverpool, University of Sheffield, and Université Libre de Bruxelles. Conflicts of interest None. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. Electronic supplementary material Below is the link to the electronic supplementary material. ESM 1 (DOC 34.5 kb) References
1. Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, Licata A, Benhamou L, Geusens P, Flowers K, Stracke H, Seeman E (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285(3):320–323PubMedCrossRef 2. Ross PD, Genant HK, Davis JW, Miller PD, Wasnich RD (1993) Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. Osteoporos Int 3(3):120–126PubMedCrossRef 3. Gartland A, Hipskind RA, Gallagher JA, Bowler WB (2001) Expression of a P2X7 receptor by a subpopulation of human osteoblasts. J Bone Miner Res 16(5):846–856PubMedCrossRef 4. Nakamura E, GSK2118436 cost Uezono Y, Narusawa K, Shibuya I, Oishi Y, Tanaka M, Yanagihara N, Nakamura T, Izumi F (2000) ATP activates DNA synthesis by acting on P2X receptors in human osteoblast-like MG-63 cells. Am J Physiol Cell Physiol 279:C510–C519PubMed 5. Henriksen Z, Nissen N, Jorgensen NR (2006) Functional P2X7 purinergic receptors are expressed in differentiated human osteoblasts. J Bone Min res abstract SU208 6.