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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.

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.

SUBMITTER: Wesselius A

PROVIDER: S-EPMC3568421 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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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.

Wesselius Anke A Bours Martijn Jl MJ Jørgensen Niklas R NR Wiley James J Gu Ben B van Helden Svenjhalmar S van Rhijn Lodewijk L Dagnelie Pieter C PC

Purinergic signalling 20121110 1

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 ) ...[more]

PMID: 23138503

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Project description:Osteoporosis, a disease characterized by low bone mineral density (BMD), increases the risk for fractures. Conventional risk factors alone do not completely explain measured BMD or osteoporotic fracture risk. Metabolomics may provide additional information. We aim to identify BMD-associated metabolomic markers that are predictive of fracture risk. We assessed 209 plasma metabolites by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 1552 Framingham Offspring Study participants, and measured femoral neck (FN) and lumbar spine (LS) BMD 2 to 10 years later using dual-energy X-ray absorptiometry. We assessed osteoporotic fractures up to 27-year follow-up after metabolomic profiling. We identified 27 metabolites associated with FN-BMD or LS-BMD by LASSO regression with internal validation. Incorporating selected metabolites significantly improved the prediction and the classification of osteoporotic fracture risk beyond conventional risk factors (area under the curve [AUC] = 0.74 for the model with identified metabolites and risk factors versus AUC = 0.70 with risk factors alone, p = .001; net reclassification index = 0.07, p = .03). We replicated significant improvement in fracture prediction by incorporating selected metabolites in 634 participants from the Hong Kong Osteoporosis Study (HKOS). The glycine, serine, and threonine metabolism pathway (including four identified metabolites: creatine, dimethylglycine, glycine, and serine) was significantly enriched (false discovery rate [FDR] p value = .028). Furthermore, three causally related metabolites (glycine, phosphatidylcholine [PC], and triacylglycerol [TAG]) were negatively associated with FN-BMD, whereas PC and TAG were negatively associated with LS-BMD through Mendelian randomization analysis. In summary, metabolites associated with BMD are helpful in osteoporotic fracture risk prediction. Potential causal mechanisms explaining the three metabolites on BMD are worthy of further experimental validation. Our findings may provide novel insights into the pathogenesis of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

Dataset Information

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

Publications

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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