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

Arthritis Rheum. 2004 Jul;50(7):2211-5. doi: 10.1002/art.20347.


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 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] 0.40-0.85). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antigens, CD
  • Antigens, Differentiation / genetics*
  • CTLA-4 Antigen
  • Case-Control Studies
  • Confidence Intervals
  • Gene Frequency
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Microsatellite Repeats
  • Odds Ratio
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length


  • 3' Untranslated Regions
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Genetic Markers