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

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. 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 fluorescence‐labeled primer. 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 [Pcorr] = 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, Pcorr = 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, Pcorr = 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.The 3′‐UTR of the CTLA4 gene is involved in susceptibility to SLE. [ABSTRACT FROM AUTHOR]