Association of P2X(7) receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients

SUMMARY: The P2X(7) receptor is thought to be involved in bone physiology in a pro-osteogenic manner. Therefore, we examined associations between genetic variations in the P2X(7) receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X(7) receptor and the risk of osteoporosis. INTRODUCTION: The purpose of this study was to determine whether genetic variation in the P2X(7) receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients. METHODS: Six hundred ninety women and 231 men aged ≥50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck. RESULTS: Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p = 0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p = 0.018 and p = 0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40 % decrease in risk of a lower T-score value (OR = 0.58 [95%CI, 0.33–1.00]). CONCLUSION: Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-012-2059-x) contains supplementary material, which is available to authorized users.