title: HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjögren's syndrome.
abstract: OBJECTIVE
  To evaluate the contribution of HLA class II region and the CTLA-4 gene in genetic susceptibility to rheumatoid arthritis (RA) and Sjögren's syndrome (SS) in the Tunisian population.
  
  
  METHODS
  The polymorphisms of a (CA)n microsatellite of HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and an (AT)n microsatellite in the 3'-untranslated region of exon 3 of the CTLA-4 gene were analysed after specific polymerase chain reaction (PCR) amplification. Typing of CTLA-4 A/G exon 1 polymorphism was achieved by the PCR-restriction fragment length polymorphism method.
  
  
  RESULTS
  Genomic DNA from 60 patients with RA, 58 patients with SS and 150 healthy individuals was genotyped. The distribution of HLA-DQ CAR1/CAR2 allele frequencies differed between patients and controls in both diseases (RA, P<10(-15); SS, P=7.6x10(-15); RA+SS, P<10(-15)). The analysis of TNFa IR2/IR4 and CTLA-4 A/G polymorphisms did not show any differences in allele or genotype frequencies between patients and control subjects in either disease. The distribution of CTLA-4 (AT)n allele frequencies differed between patients with RA and controls (P=10(-3)), whereas no significant difference was detected between patients with SS and controls.
  
  
  CONCLUSIONS
  These data suggest the involvement of HLA-DQ CAR1/CAR2 polymorphisms in genetic susceptibility to RA and SS and the participation of the CTLA-4 gene, or a gene closely associated with it, in the development of RA.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de médecine, Sfax, Tunisia.
authors.forename: H
authors.initials: H
authors.lastname: Hadj Kacem
authors.forename: N
authors.initials: N
authors.lastname: Kaddour
authors.forename: F Z
authors.initials: FZ
authors.lastname: Adyel
authors.forename: Z
authors.initials: Z
authors.lastname: Bahloul
authors.forename: H
authors.initials: H
authors.lastname: Ayadi
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012859:Sjogren's Syndrome / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014416:Tunisia
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept