Ricardo Usategui-Martín1,2, Ismael Calero-Paniagua2,3, Judith García-Aparicio2,4, Luis Corral-Gudino4, Javier Del Pino Montes2,3, Rogelio González Sarmiento1,2,5. 1. 1 Unidad de Medicina Molecular, Departamento de Medicina, Universidad de Salamanca , Salamanca, Spain . 2. 2 Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca-USAL-CSIC , Salamanca, Spain . 3. 3 Servicio de Reumatología, Hospital Universitario de Salamanca , Salamanca, Spain . 4. 4 Servicio de Medicina Interna, Hospital Universitario de Salamanca , Salamanca, Spain . 5. 5 Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Universidad de Salamanca-CSIC , Salamanca, Spain .
Abstract
BACKGROUND AND AIMS: Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The disease affects osteoclasts which increase in size, number, and activity. One of the etiopathogenic hypotheses is that the disease is genetic. It has been reported that Rho GEF Vav3 is an essential factor in the regulation of osteoclast function, and alteration of the VAV3 gene could influence the development of the disease. The aim of our study was to perform an association study between variants of the VAV3 gene and the risk of developing Paget's disease of bone. PATIENTS AND METHODS: The genotypic and allelic distribution of the VAV3 c.892A>T/p.T298S (rs7528153) polymorphism was compared between a cohort of 238 Spanish subjects with PDB and a cohort of 253 healthy subjects. RESULTS: Our results indicated that individuals carrying the VAV3 rs7528153 TT genotype were at a significantly increased risk of developing PDB (p < 0.001, odds ratio [OR] = 3.15, 95% confidence interval [95% CI] = 1.77-5.61). CONCLUSIONS: These results suggest that inheriting the VAV3 rs7528153 polymorphism is a likely susceptibility factor for developing Paget's disease of bone.
BACKGROUND AND AIMS: Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The disease affects osteoclasts which increase in size, number, and activity. One of the etiopathogenic hypotheses is that the disease is genetic. It has been reported that Rho GEF Vav3 is an essential factor in the regulation of osteoclast function, and alteration of the VAV3 gene could influence the development of the disease. The aim of our study was to perform an association study between variants of the VAV3 gene and the risk of developing Paget's disease of bone. PATIENTS AND METHODS: The genotypic and allelic distribution of the VAV3 c.892A>T/p.T298S (rs7528153) polymorphism was compared between a cohort of 238 Spanish subjects with PDB and a cohort of 253 healthy subjects. RESULTS: Our results indicated that individuals carrying the VAV3 rs7528153 TT genotype were at a significantly increased risk of developing PDB (p < 0.001, odds ratio [OR] = 3.15, 95% confidence interval [95% CI] = 1.77-5.61). CONCLUSIONS: These results suggest that inheriting the VAV3 rs7528153 polymorphism is a likely susceptibility factor for developing Paget's disease of bone.
Authors: Frederick R Singer; Barbara G Mills; Helen E Gruber; Jolene J Windle; G David Roodman Journal: J Bone Miner Res Date: 2006-12 Impact factor: 6.741
Authors: Roberta Faccio; Steven L Teitelbaum; Keiko Fujikawa; Jean Chappel; Alberta Zallone; Victor L Tybulewicz; F Patrick Ross; Wojciech Swat Journal: Nat Med Date: 2005-02-13 Impact factor: 53.440
Authors: Omar M E Albagha; Sachin E Wani; Micaela R Visconti; Nerea Alonso; Kirsteen Goodman; Maria Luisa Brandi; Tim Cundy; Pui Yan Jenny Chung; Rosemary Dargie; Jean-Pierre Devogelaer; Alberto Falchetti; William D Fraser; Luigi Gennari; Fernando Gianfrancesco; Michael J Hooper; Wim Van Hul; Gianluca Isaia; Geoff C Nicholson; Ranuccio Nuti; Socrates Papapoulos; Javier del Pino Montes; Thomas Ratajczak; Sarah L Rea; Domenico Rendina; Rogelio Gonzalez-Sarmiento; Marco Di Stefano; Lynley C Ward; John P Walsh; Stuart H Ralston Journal: Nat Genet Date: 2011-05-29 Impact factor: 38.330
Authors: Omar M E Albagha; Micaela Rios Visconti; Nerea Alonso; Sachin Wani; Kirsteen Goodman; William D Fraser; Luigi Gennari; Daniela Merlotti; Fernando Gianfrancesco; Teresa Esposito; Domenico Rendina; Marco di Stefano; Giancarlo Isaia; Maria Luisa Brandi; Francesca Giusti; Javier Del Pino-Montes; Luis Corral-Gudino; Rogelio Gonzalez-Sarmiento; Lynley Ward; Sarah L Rea; Thomas Ratajczak; John P Walsh; Stuart H Ralston Journal: J Bone Miner Res Date: 2013-11 Impact factor: 6.741