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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 &lt; 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.

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