title: Non-synonymous polymorphisms in the P2RX               (                 4               ) are related to bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients.
abstract: 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.
authors.affiliation: Department of Epidemiology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre, P O Box 616, Peter Debyeplein 1 6229HA, 6200, MD, Maastricht, The Netherlands. anke.wesselius@maastrichtuniversity.nl
authors.forename: Anke
authors.initials: A
authors.lastname: Wesselius
authors.forename: Martijn Jl
authors.initials: MJ
authors.lastname: Bours
authors.forename: Niklas R
authors.initials: NR
authors.lastname: Jørgensen
authors.forename: James
authors.initials: J
authors.lastname: Wiley
authors.forename: Ben
authors.initials: B
authors.lastname: Gu
authors.forename: Svenjhalmar
authors.initials: S
authors.lastname: van Helden
authors.forename: Lodewijk
authors.initials: L
authors.lastname: van Rhijn
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
mesh_terms: D000368:Aged; D015519:Bone Density / Q000235:genetics*; D016723:Bone Remodeling / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010024:Osteoporosis / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D058848:Receptors, Purinergic P2X4 / Q000235:genetics*; D015203:Reproducibility of Results; D012306:Risk; D012463:Saliva / Q000737:chemistry
chemical_list: C548226:P2RX4 protein, human; D058848:Receptors, Purinergic P2X4; D004247:DNA