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Non-synonymous polymorphisms in the P2RX 4 are related to bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients


In the present study we investigated whether single nucleotide polymorphisms (SNPs) in the P2RX 4 , which alter the P2X 4 R function, are associated with the development of osteoporosis and whether an interaction between the P2X 4 R and P2X 7 R confer a synergistic effect of these two receptors on osteoporosis risk. Patients with fracture (690 females and 231 males, aged ≥50 years) were genotyped for three non-synonymous P2X 4 R SNPs. Bone mineral density (BMD) was measured at the total hip, lumbar spine, and femoral neck. Subject carrying the variant allele of the Tyr315Cys polymorphism showed a 2.68-fold (95 % CI, 1.20–6.02) higher risk of osteoporosis compared with wild-type subject. Furthermore, significant lower lumbar spine BMD values were observed in subjects carrying the Cys315 allele as compared with wild-type (0.85 ± 0.17 and 0.93 ± 0.17 g/cm2, respectively; p < 0.001). Assuming a recessive model, carriers of the variant allele of the Ser242Gly polymorphism showed increased BMD values at the lumbar spine compare to wild-type subject (1.11 ± 0.35 and 0.92 ± 0.17 g/cm2, respectively; p = 0.0045). This is the first study demonstrating an association of non-synonymous polymorphisms in the P2RX 4 and the risk of osteoporosis, suggesting a role of the P2X 4 R in the regulation of bone mass.

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The work was supported by the European Commission under the 7th Framework Programme, performed as a collaborative project “Fighting Osteoporosis by blocking nucleotides: purinergic signaling in bone formation and homeostasis” (ATPBone), with participants; Copenhagen University Hospital, University College London, Maastricht University, University of Ferrara, University of Liverpool, University of Sheffield, and Université Libre de Bruxelles.

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Correspondence to Anke Wesselius.

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Wesselius, A., Bours, M.J., Jørgensen, N.R. et al. Non-synonymous polymorphisms in the P2RX 4 are related to bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients. Purinergic Signalling 9, 123–130 (2013). https://doi.org/10.1007/s11302-012-9337-0

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  • P2X 4 receptor
  • Osteoporosis
  • Bone mineral density
  • Polymorphisms