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) n in the 3-UTR was performed using PCR with a fluorescencelabeled 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] 0.40-0.85). 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) >19 ;CT60G. Conclusion. The 3-UTR of the CTLA4 gene is involved in susceptibility to SLE.