Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

Alison Gartland, Kristen K. Skarratt, Lynne J. Hocking, Claire Parsons, Leanne Stokes, Niklas Rye Jorgensen, William D. Fraser, David M. Reid, James A. Gallagher, James S. Wiley

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58 Citations (Scopus)


The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) for the above SNPs. Lumbar spine BMD was measured at baseline and at 6-7 year follow-up. P2RX7 genotyping was performed by homogeneous mass extension. We found association of c.946A (p.Arg307Gln) with lower LS-BMD at baseline (P=0.004, beta=-0.12) and follow-up (P=0.002, beta=-0.13). Further analysis showed that a combined group of subjects who had LOF SNPs (n=48) had nearly ninefold greater annualised percent change in LS-BMD than subjects who were wild type at the six SNP positions (n=84; rate of loss=-0.94%/year and -0.11%/year, respectively, P=0.0005, unpaired t-test). This is the first report that describes association of the c.946A (p.Arg307Gln) LOF SNP with low LS-BMD, and that other LOF SNPs, which result in reduced or no function of the P2X7 receptor, may contribute to accelerated bone loss. Certain polymorphic variants of P2RX7 may identify women at greater risk of developing osteoporosis. European Journal of Human Genetics (2012) 20, 559-564; doi:10.1038/ejhg.2011.245; published online 11 January 2012

Original languageEnglish
Pages (from-to)559-564
Number of pages6
JournalEJHG : European journal of human genetics : the official journal of the European Society of Human Genetics.
Issue number5
Publication statusPublished - May 2012


  • P2RX7
  • LS-BMD
  • single-nucleotide polymorphisms
  • human P2X(7) receptor
  • protein-kinase-C
  • lysophosphatidic acid
  • in-vitro
  • regional osteoperosis
  • recruitment methods
  • screening programs
  • osteoblatic cells
  • binding-site
  • kappa-B


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