Association of the CT60 marker of the CTLA4 gene with systemic lupus erythematosus

Objective. To investigate the possible association of the CT60A/G marker with systemic lupus erythematosus (SLE) in Spanish patients, and to identify the possible CTLA4 haplotype responsible for the association, taking into account other polymorphisms described at positions -1722T/C, -319C/T, +49A/G, and the microsatellite (AT)(n) in the 3'-untranslated region (3'-UTR) of the CTLA4 gene. Methods. Genotyping of CT60 was performed in 395 patients with SLE and 293 healthy controls using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. Genotyping of the rest of the dimorphisms has been previously reported. Genotyping of microsatellite polymorphism (AT),, in the 3'-UTR was performed using PCR with a fluorescence-labeled primer. Results. With regard to CT60A/G, the frequency of the AA genotype was significantly decreased among the SLE patients (18.7% versus 28.3% in the control group; P = 0.003, corrected P[P-corr] = 0.009, odds ratio [OR] = 0.58, 95% confidence interval [95% CI] 0.400.85). In other words, the frequency of individuals bearing the G phenotype was increased in the patient group compared with the control group (81.2% versus 71.7%; P = 0.003, P-corr = 0.006, OR = 1.71, 95% CI 1.18-2.49). The distribution of allele frequency was also significantly different between patients and controls (P = 0-01, P-corr = 0.02, OR [for allele G] = 1.32, 95% CI 1.06-1.65). After combining the data on the different polymorphisms, 2 neutral haplotypes were found: +49A;(AT)(7) ;CT60A and +49G;(AT)(8-19);CT60G. In addition, a susceptibility haplotype was found: +49A; (AT),;CT60G. Conclusion. The 3'-UTR of the CTLA4 gene is involved in susceptibility to SLE.