ECTS2013 Poster Presentations Genetics (17 abstracts)
A genomic and transcriptomic approach to the high bone mass phenotype: evidences of heterogeneity and of additive effects of TWIST1, IL6R, DLX3, and PPARG
Patricia Sarrión 1 , Leonardo Mellibovsky 2 , Roser Urreizti 1 , Sergi Civit 3 , Neus Cols 1 , Natàlia García-Giralt 2 , Guy Yoskovitz 2 , Alvaro Aranguren 1 , Jorge Malouf 4 , Luís del Río 5 , Roberto Güerri 2 , Xavier Nogués 2 , Adolfo Díez-Pérez 2 , Daniel Grinberg 1 & Susana Balcells 1
1Departament de Genètica, Universitat de Barcelona, IBUB, CIBERER, Barcelona, Spain; 2URFOA, IMIM, Hospital del Mar, RETICEF, Barcelona, Spain; 3Departament de Estadística, Universitat de Barcelona, Barcelona, Spain; 4Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 5CETIR Medical Imaging Center, Barcelona, Spain.
The aims of this study were to establish the prevalence of the high bone mass (HBM) phenotype in a cohort of Spanish postmenapausal women (BARCOS); to determine whether any of the HBM cases carry LRP5 or DKK1 mutations; to test the hypothesis of an inverse correlation between the number of common variant risk alleles and HBM; and to characterize the expression of osteoblast-specific and Wnt pathway genes in primary osteoblast RNA samples from two HBM cases.
HBM individuals within the BARCOS cohort were identified according to the criterion of a sum Z-score >4. Relevant exons of LRP5 and DKK1 were PCR-amplified and sequenced. Fifty-five BMD SNPs from Estrada et al (NatGenet 44:491–501,2012) were genotyped in the HBM cases and a weighted score was obtained for each individual. Scores were plotted against Z-score values. Primary osteoblasts from two HBM and five controls were cultured and RNA was extracted. A qPCR Custom Panel was used to analyse the expression of 88 osteoblast-specific and/or Wnt pathway genes.
A 0.7% of individuals displayed Z-score values in the HBM range (11/1600). No mutations in the LRP5 gene were found in these women and one had a rare missense change in DKK1 (p.Y74F). Regarding risk alleles, results pointed to an inverse correlation between those and Z-scores in the HBM group of women, although the woman with the highest Z-score presented with the highest risk score. A low frequency penetrant unknown genetic variant may explain this case. Finally, the expression analysis showed that levels of IL6R, DLX3, TWIST1, and PPARG mRNA were inversely related to Z-score and that one HBM case presented with high levels of RUNX2 while the other displayed very low SOX6.
In conclusion, we provide evidences of heterogeneity and of additive effects of TWIST1, IL6R, DLX3, and PPARG for the HBM phenotype.
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Bone Abstracts
ISSN 2052-1219 (online)
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