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Rheumatology 2001; 40: 1370-1374
© 2001 British Society for Rheumatology


Original Papers

HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjögren's syndrome

H. Hadj Kacem, N. Kaddour1, F.-Z. Adyel, Z. Bahloul1 and H. Ayadi

Laboratoire de Génétique Moléculaire Humaine, Faculté de médecine, Sfax and
1 Service de médecine interne CHU Hédi Chaker, Sfax, Tunisia

Objectives. 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.

Conclusion. 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.

KEY WORDS: HLA-DQ CAR, TNF, CTLA-4, Association, Polymorphism, Rheumatoid arthritis, Sjögren's syndrome.

Correspondence to: H. Ayadi, Faculté de Médecine, Laboratoire de Génétique Moléculaire Humaine, Av. Majida Boulila 3029, Sfax, Tunisia


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