000046547 001__ 46547
000046547 005__ 20210121114535.0
000046547 0247_ $$2doi$$a10.1371/journal.pone.0126153
000046547 0248_ $$2sideral$$a93305
000046547 037__ $$aART-2015-93305
000046547 041__ $$aeng
000046547 100__ $$aGervas-Arruga, J.
000046547 245__ $$aThe influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease
000046547 260__ $$c2015
000046547 5060_ $$aAccess copy available to the general public$$fUnrestricted
000046547 5203_ $$aGaucher disease, the most common lysosomal storage disorder, is caused by ß-glucocerebrosidase deficiency. Bone complications are the major cause of morbidity in patients with type 1 Gaucher disease (GD1). Genetic components strongly influence bone remodelling. In addition, chronic inflammation produced by Gaucher cells induces the production of several cytokines, which leads to direct changes in the bone remodelling process and can also affect the process indirectly through other immune cells. In this study, we analysed the association between bone mineral density (BMD), bone marrow burden score, and relevant genetic polymorphisms related to bone metabolism, as well as profiles of proinflammatory cytokines in a GD1 cohort. This study included 83 patients distributed according to bone status. BMD was measured with DXA and broadband ultrasound attenuation; bone marrow involvement was evaluated using MRI. We also analysed 26 SNPs located in 14 genes related to bone metabolism. To assess proinflammatory status, we analysed IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1a, MIP-1ß, and TNFa in plasma samples from 71 control participants and GD1 patients. SNP genotype proportions and BMD differed significantly between ESRI c.453-397T>C and VDR c.1024+283G>A variants. We also observed significant associations between GD1 genotypes and bone affectation. When patients were stratified by spleen status, we observed significant correlations between non-/splenectomized groups and Spanish MRI (S-MRI) score. Across genotype proportions of non-/splenectomized patients and S-MRI, we observed significant differences in ESRI c.453-397T>C, VDR c.-83-25988G>A, and TNFRSF11B c.9C>G polymorphisms. We observed different significant proinflammatory profiles between control participants, treatment-naive patients, and patients on enzyme replacement therapy (ERT); between non-/splenectomized patients (between untreated and ERT-treated patients) and among those with differing GBA genotypes. The data suggest that patients with GD1 have increased susceptibility to developing bone disease owing to the coexistence of genetic variants, and that genetic background in GD1 is fundamental to regulate the impact of proinflammatory status on the development of bone disease.
000046547 536__ $$9info:eu-repo/grantAgreement/ES/FIS/FIS09-02556$$9info:eu-repo/grantAgreement/ES/FIS/PI12-01219
000046547 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000046547 590__ $$a3.057$$b2015
000046547 591__ $$aMULTIDISCIPLINARY SCIENCES$$b11 / 62 = 0.177$$c2015$$dQ1$$eT1
000046547 592__ $$a1.427$$b2015
000046547 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2015$$dQ1
000046547 593__ $$aMedicine (miscellaneous)$$c2015$$dQ1
000046547 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2015$$dQ1
000046547 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000046547 700__ $$aCebolla, J.J.
000046547 700__ $$0(orcid)0000-0002-1204-4356$$aDe Blas, I.$$uUniversidad de Zaragoza
000046547 700__ $$aRoca, M.
000046547 700__ $$0(orcid)0000-0001-8807-9187$$aPocovi, M.$$uUniversidad de Zaragoza
000046547 700__ $$0(orcid)0000-0002-8791-1901$$aGiraldo, P.
000046547 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000046547 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000046547 773__ $$g10, 5 (2015), 0126153[15 pp]$$pPLoS One$$tPloS one$$x1932-6203
000046547 8564_ $$s1364477$$uhttps://zaguan.unizar.es/record/46547/files/texto_completo.pdf$$yVersión publicada
000046547 8564_ $$s112005$$uhttps://zaguan.unizar.es/record/46547/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000046547 909CO $$ooai:zaguan.unizar.es:46547$$particulos$$pdriver
000046547 951__ $$a2021-01-21-11:13:12
000046547 980__ $$aARTICLE