title: Polymorphisms in autophagy genes are associated with paget disease of bone.
abstract: Paget disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The main alteration resides in osteoclasts that increase in size, number and activity. Many osteoclasts have cytoplasmic inclusions that have been associated with protein aggregates, increasing the evidences of a possible deregulation of autophagy in the development of the PDB. Autophagy starts with encapsulation of the target into a double-membrane-bound structure called an "autophagosome." It has been reported that at least 18 ATG genes (autophagy-related genes) are involved in autophagosome formation. We have studied the distribution of genotypes of the ATG2B rs3759601, ATG16L1 rs2241880, ATG10 rs1864183 and ATG5 rs2245214 polymorphisms in a Spanish cohort of subjects with PDB and compared with healthy subjects. Our results show that being a carrier of the C allele of the ATG16L1 rs2241880 and the G allele of ATG5 rs2245214 polymorphisms were associated with an increased risk of developing PDB, whereas being a carrier of the T allele of ATG10 rs1864183 polymorphism decreased the risk of suffering the disease in our series. This is the first report that shows an association between autophagy and Paget Disease of Bone and requires further confirmation in other series.
authors.affiliation: Unidad de Medicina Molecular-IBSAL, Departamento de Medicina, Universidad de Salamanca-Hospital Universitario de Salamanca-CSIC, Salamanca, España.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Usategui-Martín
authors.affiliation: Servicio de Medicina interna-IBSAL, Hospital Universitario de Salamanca Universidad de Salamanca CSIC, Salamanca, España.
authors.forename: Judith
authors.initials: J
authors.lastname: García-Aparicio
authors.affiliation: Servicio de Medicina interna-IBSAL, Hospital Universitario de Salamanca Universidad de Salamanca CSIC, Salamanca, España.
authors.forename: Luis
authors.initials: L
authors.lastname: Corral-Gudino
authors.affiliation: Servicio de Reumatología-IBSAL, Hospital Universitario de Salamanca-Universidad de Salamanca-CSIC, Salamanca, España.
authors.forename: Ismael
authors.initials: I
authors.lastname: Calero-Paniagua
authors.affiliation: Servicio de Reumatología-IBSAL, Hospital Universitario de Salamanca-Universidad de Salamanca-CSIC, Salamanca, España.
authors.forename: Javier
authors.initials: J
authors.lastname: Del Pino-Montes
authors.affiliation: Unidad de Medicina Molecular-IBSAL, Departamento de Medicina, Universidad de Salamanca-Hospital Universitario de Salamanca-CSIC, Salamanca, España; Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Universidad de Salamanca-CSIC, Salamanca, España.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González Sarmiento
mesh_terms: D000483:Alleles; D001343:Autophagy / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000209:etiology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010001:Osteitis Deformans / Q000209:etiology / Q000235:genetics*; D010010:Osteoclasts / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk