title: Association of CD28 IVS3 +17T/C polymorphism with soluble CD28 in rheumatoid arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity.
  
  
  METHODS
  We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.
  
  
  RESULTS
  RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02-2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p =0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p =0.016), was found.
  
  
  CONCLUSIONS
  The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.
authors.affiliation: Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: I Y
authors.initials: IY
authors.lastname: Ledezma-Lozano
authors.forename: J J
authors.initials: JJ
authors.lastname: Padilla-Martínez
authors.forename: S D
authors.initials: SD
authors.lastname: Leyva-Torres
authors.forename: I
authors.initials: I
authors.lastname: Parra-Rojas
authors.forename: M G
authors.initials: MG
authors.lastname: Ramírez-Dueñas
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Pereira-Suárez
authors.forename: H
authors.initials: H
authors.lastname: Rangel-Villalobos
authors.forename: S L
authors.initials: SL
authors.lastname: Ruiz-Quezada
authors.forename: P E
authors.initials: PE
authors.lastname: Sánchez-Hernández
authors.forename: J F
authors.initials: JF
authors.lastname: Muñoz-Valle
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D018106:CD28 Antigens / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D018106:CD28 Antigens