Polymorphisms of CTLA-4 Exon 1 and Promoter Genes in Systemic Lupus Erythematosus and Rheumatoid Arthritis

Lee, Young Ho; Choi, Seong Jae; Kim, Ye Ree; Ji, Jong Dae; Song, Gwan Gyu

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.