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Genetic Analysis of High Bone Mass Cases from the BARCOS Cohort of Spanish Postmenopausal Women
Sarrion, Patricia (Universitat de Barcelona. Departament de Genètica)
Mellibovsky, Leonardo (Hospital del Mar (Barcelona, Catalunya))
Urreizti, Roser (Universitat de Barcelona. Departament de Genètica)
Civit, Sergi (Universitat de Barcelona. Departament d'Estadística)
Cols, Neus (Universitat de Barcelona. Departament de Genètica)
García Giralt, Natalia (Hospital del Mar (Barcelona, Catalunya))
Yoskovitz, Guy (Hospital del Mar (Barcelona, Catalunya))
Aranguren, Álvaro (Universitat de Barcelona. Departament de Genètica)
Malouf, Jorge (Hospital de la Santa Creu i Sant Pau)
Di Gregorio, Silvana (Instituto de Salud Carlos III)
del Rio, Luís (Instituto de Salud Carlos III)
Güerri Fernández, Roberto (Hospital del Mar (Barcelona, Catalunya))
Nogués Solan, Xavier (Hospital del Mar (Barcelona, Catalunya))
Díez Pérez, Adolfo (Hospital del Mar (Barcelona, Catalunya))
Grinberg, Daniel (Universitat de Barcelona. Departament de Genètica)
Balcells, Susana (Universitat de Barcelona. Departament de Genètica)

Data: 2014
Resum: The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0. 6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p. Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: Osteoblasts ; Mutation ; Gene expression ; Alleles ; Bone density ; Phenotypes ; Polymerase chain reaction ; Genotyping
Publicat a: PLoS one, Vol. 9 Issue 4 (April 2014) , p. e94607, ISSN 1932-6203

DOI: 10.1371/journal.pone.0094607

9 p, 869.4 KB

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