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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

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  • Anke Wesselius
  • Martijn Jl Bours
  • Niklas R Jørgensen
  • James Wiley
  • Ben Gu
  • Svenjhalmar van Helden
  • Lodewijk van Rhijn
  • Pieter C Dagnelie
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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/cm(2), 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/cm(2), 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.

Original languageEnglish
JournalPurinergic Signalling
Volume9
Issue number1
Pages (from-to)123-30
Number of pages8
ISSN1573-9538
DOIs
Publication statusPublished - Mar 2013

    Research areas

  • Aged, Bone Density, Bone Remodeling, Cohort Studies, DNA, Female, Fractures, Bone, Genotype, Haplotypes, Humans, Linkage Disequilibrium, Male, Middle Aged, Netherlands, Osteoporosis, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Receptors, Purinergic P2X4, Reproducibility of Results, Risk, Saliva

ID: 43540471