ABSTRACT
OBJECTIVE: Strong genetic evidence has shown an association between cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and autoimmune diseases. This study was set out to determine whether the polymorphisms of the CTLA-4 exon 1 and promoter are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and their clinical features. METHODS: Polymerase chain reaction of genomic DNA-restriction fragment length polymorphism using Bst E II and Tru9 I was used to determine genotypes of the CTLA-4 exon 1 and promoter in 80 SLE, 86 RA patients and 86 healthy control subjects. Clinical manifestations were analyzed in each patient and correlated with the genotypes. RESULTS: The genotype frequency of the CTLA-4 exon 1 differed between SLE patients and controls (chi-squared=.74, 2 degrees of freedom (df), p=.03). The CTLA-4 AG genotype occurred more frequently in patients with SLE (46.3% vs. 33.7% controls). On the other hand, the CTLA-4 AA genotype as well as the CTLA-4 GG genotype was less frequent among SLE patients than among control subjects (1.3% vs. 9.3% and 52.5% vs. 57.0% respectively). The genotype distribution of the CTLA-4 promoter differed between SLE patients and control subjects (CT, TT, CC genotypes 27.5%, 0%, 72.5% vs. 16.3%, 4.7%, 79.1% controls respectively, chi-squared=.36, 2 df, p=0.04). When the association was analyzed with respect to sex, the distribution of the CTLA-4 exon 1- promotor genotypes was significantly different between female SLE patients and females in the control group (chi-squared=8.16, 3 df, p=0.04). The frequencies of the CTLA-4 exon 1 and promoter genotypes, allele and phenotypes and exon 1-promotor genotypes were not significantly different between RA patients and control subjects. Clinically, there were no significant differences in patients with SLE and RA according to the CTLA-4 polymorphisms. CONCLUSION: The polymorphisms within the CTLA-4 exon 1 and promoter appear to play a role in susceptibility to SLE, but not to be associated with clinical features of SLE, susceptibility to RA and its clinical features.