title: KIR2DL2 and KIR2DS2 as genetic markers to the methotrexate response in rheumatoid arthritis patients.
abstract: BACKGROUND
  Disease Modifying Anti-Rheumatic Drugs (DMARDs) are aimed to interfere with rheumatoid arthritis (RA) progression and reduce the joint damage; however, not all patients respond alike. Killer-cell immunoglobulin-like receptors (KIR) and their ligands, human leucocyte antigen class I (HLA-I), have been associated with RA pathology; therefore, KIR and HLA genes may influence the treatment response.
  
  
  METHODS
  We evaluated the association of KIR genotype and their ligands HLA-C genes with the response to DMARDs in RA patients. We included 69 patients diagnosed with RA and 82 healthy individuals as the reference group. KIR and HLA-C genotyping was performed using SSP-PCR. RA patients were assessed at baseline and under treatment at 6 and 12 months; subsequently classified as responders and non-responders in each time period. We evaluated the association between DMARD response and genes using statistical analysis by using Fisher exact test with Bonferroni correction; results were regarded as statistically significant at p < 0.05.
  
  
  RESULTS
  Significant difference was observed in gene frequencies of patients and the reference group, KIR2DL2 was associated with RA (p = 0.031, OR = 2.119). We also observed an association between KIR2DS2 and the response to methotrexate (MTX), moreover, the combination KIR2DL2+/KIR2DS2+ was more frequent in responders to MTX (p = 0.043).
  
  
  CONCLUSIONS
  In our results, responders and non-responders to DMARDs showed KIR2DS2 and KIR2DL2 different gene frequencies, therefore, these genes could be used as response predictors to DMARDs treatment. Thus, these genes were also associated with disease severity, as well as the treatment response possibly by the immunoregulatory function of NK cells.
authors.affiliation: a Laboratorio de Inmunología, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;|b Doctorado en Ciencias Biomédicas, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: Erandi Enif
authors.initials: EE
authors.lastname: Velarde-de la Cruz
authors.affiliation: a Laboratorio de Inmunología, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;|b Doctorado en Ciencias Biomédicas, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: Pedro Ernesto
authors.initials: PE
authors.lastname: Sánchez-Hernández
authors.affiliation: b Doctorado en Ciencias Biomédicas, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;|c Instituto de Investigación en Ciencias Biomédicas, Departamento de Biología Molecular y Genómica , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
authors.affiliation: b Doctorado en Ciencias Biomédicas, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;|c Instituto de Investigación en Ciencias Biomédicas, Departamento de Biología Molecular y Genómica , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: Claudia Azucena
authors.initials: CA
authors.lastname: Palafox-Sánchez
authors.affiliation: d Departamento de Clínicas , Centro Universitario de los Altos, Universidad de Guadalajara , Tepatitlán , Jalisco , México.
authors.forename: Saúl
authors.initials: S
authors.lastname: Ramírez-de Los Santos
authors.affiliation: a Laboratorio de Inmunología, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;|b Doctorado en Ciencias Biomédicas, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: Omar
authors.initials: O
authors.lastname: Graciano-Machuca
authors.affiliation: a Laboratorio de Inmunología, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: Trinidad
authors.initials: T
authors.lastname: García-Iglesias
authors.affiliation: a Laboratorio de Inmunología, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: Margarita
authors.initials: M
authors.lastname: Montoya-Buelna
authors.affiliation: a Laboratorio de Inmunología, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;|b Doctorado en Ciencias Biomédicas, Departamento de Fisiología , Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara , Jalisco , México ;
authors.forename: María Guadalupe
authors.initials: MG
authors.lastname: Ramírez-Dueñas
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D054343:Receptors, KIR2DL2 / Q000235:genetics* / Q000276:immunology
chemical_list: D005819:Genetic Markers; C515077:KIR2DL2 protein, human; C433932:KIR2DS2 protein, human; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D008727:Methotrexate
keywords: Autoimmunity; DMARDs; KIR genes; pharmacogenetics; treatment response