title: PTPN22 is not associated with Behçet's disease. Study spanning the complete gene region in the Spanish population and meta-analysis of the functional variant R620W.
abstract: The functional variant R620W of the protein tyrosine phosphatase non receptor-22 (PTPN22) gene plays an important role in susceptibility to several immuno-mediated pathologies. Behçet's disease (BD) is a complex disease related to the immune system with a demonstrated genetic base. The HLA class I genes are the most important genetic factors in BD although other genes are also involved in the susceptibility to this disease. The PTPN22 has been proposed as a candidate gene in BD but this association has not been clearly demonstrated yet. The aim of this study was to assess the association of PTPN22 with BD.
  
  
  
  A cohort composed of 404 Spanish BD patients and 1517 unrelated healthy individuals ethnically matched was genotyped in rs2476601 (R620W). Five tag SNPs: rs1217412, rs2476599, rs3789607, rs3765598 and rs1217419 (spanning a 57 Kb region between 3'UTR and 5'UTR) and rs2488457 (located at the promoter region) were also studied in order to perform a screening of the complete gene. Genotyping was performed using TaqMan® assays. The rs2476601 data were included in a meta-analysis together with those published till the date. The rest of SNPs were used in a case-control study.
  
  
  
  No evidence of the association of rs2476601 with BD in the meta-analysis (P = 0.504 in the model of alleles) was found. In the case-control study, no statistically significant differences were observed when comparing the distribution of variants in patients and controls.
  
  
  
  Our results do not support a major role of the PTPN22 gene in BD.
authors.affiliation: Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ortiz-Fernández
authors.affiliation: Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Montes-Cano
authors.affiliation: Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
authors.forename: José-Raúl
authors.initials: JR
authors.lastname: García-Lozano
authors.affiliation: Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Conde-Jaldón
authors.affiliation: Servicio de Medicina Interna, Hospital Clínico San Cecilio, Granada, Spain.
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.affiliation: Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: González-Leon
authors.affiliation: Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.affiliation: Servicio de Reumatología, Complejo Hospitalario Universitario, A Coruña, Spain.
authors.forename: Genaro
authors.initials: G
authors.lastname: Graña-Gil
authors.affiliation: Servicio de Reumatología, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sánchez-Bursón
authors.affiliation: Servei d´Inmunología. Hospital Universitari Son Espases, Palma de Mallorca, Spain.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Juliá
authors.affiliation: Servicio de Medicina Interna, Hospital Vall d´Hebron, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Solans
authors.affiliation: Servicio de Reumatología, Hospital Marqués de Valdecilla, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Servicio de Medicina Interna, Hospital de Torrecárdenas, Almería, Spain.
authors.forename: Ana-Celia
authors.initials: AC
authors.lastname: Barnosi-Marín
authors.affiliation: Servicio de Medicina Interna, Hospital Virgen del Camino, Pamplona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fanlo
authors.affiliation: Servicio de Medicina Interna, Hospital Universitari Mútua, Terrassa, Barcelona, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Rodríguez Carballeira
authors.affiliation: Servicio de Medicina Interna, Hospital Universitario Carlos Haya, Málaga, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Camps
authors.affiliation: Servicio de Reumatología, Hospital de la Princesa, Madrid, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.affiliation: Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain. mariaf.gonzalez.sspa@juntadeandalucia.es.
authors.forename: María Francisca
authors.initials: MF
authors.lastname: González-Escribano
mesh_terms: D001528:Behcet Syndrome / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors; D013030:Spain
chemical_list: D005819:Genetic Markers; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22