ECTS2013 Poster Presentations Genetics (17 abstracts)
Gene-wide association study of RANK and RANKL genes in the bone context: functional study of BMD-associated SNPs
Natalia Garcia-Giralt 1 , Guy Yoskovitz 1 , Maria Rodriguez-Sanz 1 , Roser Urreizti 2 , Roberto Guerri 1, , Sergi Ariño-Ballester 1 , Daniel Prieto-Alhambra 1, , Leonardo Mellibovsky 1, , Daniel Grinberg 2 , Xavier Nogues 1, , Susana Balcells 2 & Adolfo Diez-Perez 1,
1Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), RETICEF, Barcelona, Catalonia, Spain; 2Departament de Genètica, Universitat de Barcelona, IBUB, CIBERER, ISCIII, Barcelona, Catalonia, Spain; 3Servei de Medicina Interna, Hospital del Mar, Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain; 4NIHR Biomedical Research Unit, University of Oxford, Oxford, UK.
Over the past decade, many GWAs and meta-analyses were performed to identify genes and regions involved in bone metabolism and in the osteoporotic phenotypes. Nevertheless, the majority of these GWAS results were not tested at any functional level. This study aims to find and study functional regions in the RANK and RANKL genes that encode well-established proteins in the bone remodeling equilibrium. SNPs, chosen for their location in an evolutionary conserved region or replicated from previous studies, were genotyped in the BARCOS cohort of 1098 postmenopausal women. SNP rs9594738, which lies 184 bp upstream of the RANKL gene, was found to be associated with lumbar spine bone mineral density (Log additive model: beta coefficient=−0.021, P=3.8×10−4). Functional experiments exploring this RANKL distal region (DR) harboring rs9594738 demonstrated the region’s capacity to inhibit the RANKL promoter in reporter gene assays. Moreover, DR was activated in vitamin D presence. In conclusion, our results demonstrate DR functionality in the RANKL gene context, with a vitamin D involvement.
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Bone Abstracts
ISSN 2052-1219 (online)
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