Human Genetics

, Volume 116, Issue 5, pp 361–367 | Cite as

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis

  • Young Ho Lee
  • John B. Harley
  • Swapan K. Nath
Original Investigation


Several reports demonstrate association between variants of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune diseases. CTLA-4 may generate autoimmunity by immune dysregulation, making CTLA-4 an attractive candidate gene for systemic lupus erythematosus (SLE) susceptibility. Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 14 independent studies (to July 2004) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at four polymorphic sites found in exon-1 (at +49), the promoter region (at −318 and −1722), and the 3′ untranslated region (3′UTR) (dinucleotide repeat). We have evaluated both fixed and random effect models, depending on the presence of between-study heterogeneity. The data demonstrate that the exon-1 +49 polymorphism is significantly associated with SLE susceptibility. The overall risk, measured by odds ratio (OR), for exon-1 +49 GG genotype is 1.287 [95% confidence interval (CI)=1.031–1.562, P=0.011]. Stratification by ethnicity indicates the exon–1 +49 GG genotype is associated with SLE, at least in Asians (OR=1.293, 95% CI=1.031–1.620, P=0.026). European-derived populations have an effect of similar magnitude (OR=1.268, 95% CI=0.860–1.870, P=0.230), though not significant. Similar trends are found in allele-specific risk estimates and disease association. The OR for the exon-1 +49 risk allele (G) in Asians is 1.246 (95% CI=1.057–1.469, P=0.009), while Europeans have no evidence of allelic association (OR=0.978, 95% CI=0.833–1.148, P=0.780). In conclusion, this meta-analysis supports the CTLA-4 exon-1 +49 (A/G) polymorphism influencing the risk for developing SLE, especially in Asians.


Systemic Lupus Erythematosus Publication Bias Celiac Disease Systemic Lupus Erythematosus Patient Polymorphic Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by the National Institutes of Health (AR048928, AI063622, RR020143, AR049084, AI24717, AR42460, AR48940, AI053747, AR12253, DE15223, RR01577, RR14467) and the US Department of Veterans Affairs. We thank Ms. Summer Frank for proofreading the manuscript.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Young Ho Lee
    • 1
  • John B. Harley
    • 1
    • 2
    • 3
    • 4
  • Swapan K. Nath
    • 1
    • 2
    • 3
  1. 1.Arthritis and Immunology Research ProgramOklahoma Medical Research FoundationOklahoma CityUSA
  2. 2.Genetic Epidemiology UnitOklahoma Medical Research FoundationOklahoma CityUSA
  3. 3.University of Oklahoma Health Sciences CenterOklahoma CityUSA
  4. 4.US Department of Veterans Affairs Medical CenterOklahoma CityUSA

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