Journal of
Medical Genetics and Genomics

  • Abbreviation: J. Med. Genet. Genomics
  • Language: English
  • ISSN: 2141-2278
  • DOI: 10.5897/JMGG
  • Start Year: 2009
  • Published Articles: 48

Full Length Research Paper

Genotyping CTLA-4 exon 1 (+49 A/G) and HLA-DRB1 polymorphisms and susceptibility to systemic lupus and rheumatoid arthritis in Tunisian population

Imen Sfar1*, Tarak Dhaouadi1, Henda Krichen1, Asma Elbeldi1, Leila Abdelmoula2, Mouna Makhlouf1, Thouraya Ben Romdhane1, Salwa Jendoubi-Ayed1, Houda Aouadi1, Taieb Ben Abdallah1, Khaled Ayed1, Rafik Zouari2 and Yousr Lakhoua-Gorgi1
1Laboratory of immunology (Laboratoire de recherche LR03SP01), Charles Nicolle Hospital, Tunis, Tunisia. 2Department of Rheumatology, Charles Nicolle Hospital, Tunis, Tunisia
Email: [email protected]

  •  Accepted: 06 October 2009
  •  Published: 31 January 2010


Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a negative regulator of T-cell function, which has been suggested to be involved in a wide-range susceptibility to autoimmune diseases. We sought a probable implication of the CTLA-4 polymorphism (A/G +49) in two autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and its possible interaction with HLA-DRB1 polymorphism. CTLA-4 gene polymorphism A/G in exon 1 (+49) was analyzed by PCR-RFLP method in 78 patients with SLE, 132 with RA and 110 normal controls. HLA-DRB1 typing was performed by PCRSSP (one lambda®) in only 46 SLE patients, the 132 RA patients and 100 normal controls. The results showed that there were no significant differences in exon 1 gene of CTLA-4 polymorphism between SLE, RA and controls. HLA-DRB1*03 and DRB1*15 were significantly more frequent in SLE patients than in controls (p = 0.0001, OR (95% CI) = 4.35 (1.94 - 9.86) and p = 0.01, OR (95% CI) = 3.24 (1.28 - 8.24) respectively). In addition, the frequencies of DRB1*04 and its subtype DRB1*0405 were statistically higher in RA patients than in controls (p = 0.00043, OR (95% CI) = 2.79 (1.54 - 5.07) and p = 0.0001, OR (95% CI) = 5.65 (2.14 - 15.74) respectively). No association between CTLA-4 and HLA-DRB1 polymorphisms was observed in either SLE or RA patients. In conclusion, the CTLA-4 exon 1 polymorphism does not appear to interfere with susceptibility to SLE and RA in Tunisian patients. Corresponding with data in other populations, HLA-DRB1 seems to play major role in conferring susceptibility to SLE and RA.
Key words: Autoimmune diseases, autoimmunity, genetic polymorphism, systemic lupus erythematosus,
rheumatoid arthritis.


CTLA-4; Cytotoxic T lymphocyte antigen 4, SLE; systemic lupus erythematosus, RA; rheumatoid arthritis, ACR; American College of Rheumatology, ECLAM; European Consensus Lupus Activity Measurement, SLICC; Systemic Lupus international Collaborating Clinics/ ACR damage index for systemic lupus erythematosus, DAS28; disease activity score, RF; rheumatoid factor, Anti-CCP; anti-cyclic citrullinated peptide autoantibodies, SE; shared epitope, ICs; immune complexes, SNP; single nucleotide polymorphism.