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CTLA-4 gene polymorphisms and systemic lupus erythematosus in a population-based study of whites and African-Americans in the southeastern United States

National Institute of Environmental Health Sciences, NIH, DHHS, Durham, NC, USA, parks{at}niehs.nih.gov

L L Hudson

Medical University of South Carolina, Charleston, SC, USA

G S Cooper

National Institute of Environmental Health Sciences, NIH, DHHS, Durham, NC, USA

M A Dooley

University of North Carolina Medical School, Chapel Hill, NC, USA

E L Treadwell

East Carolina University School of Medicine, Greenville, NC, USA

E W St Clair

Duke University Medical Center, Durham, NC, USA

G S Gilkeson

Medical University of South Carolina, Charleston, SC, USA

J P Pandey

Medical University of South Carolina, Charleston, SC, USA

Cytotoxic lymphocyte antigen-4 (CTLA-4) plays an important role in regulating T cell activation, and may help to limit T cell response under conditions of inflammation. Genetic variability in CTLA-4 has been implicated in the development of several autoimmune diseases. Some studies have described associations between CTLA-4 polymorphisms and systemic lupus erythematosus (SLE), but findings have been inconsistent. We examined polymorphisms in the CTLA-4 gene promoter region (21722T/C, 21661A/G, 2318C/T) and exon 1 (+49G/A) with respect to SLE in a population-based case-control study in the southeastern US. Genotypes from 230 recently diagnosed cases and 276 controls were examined separately for African-Americans and whites. We observed no overall associations between SLE and the four CTLA-4 polymorphisms examined. Subgroup analyses revealed effect modification by age for the presence of the 21661G allele, yielding a significant positive association with SLE in younger (35 years) African-Americans (OR = 3.3). CTLA-4 genotypes also interacted with HLA-DR2 and GM allotype to contribute to risk of SLE. These findings suggest allelic variation in this region of CTLA-4 is not a major independent risk factor for SLE, but may contribute to risk of disease in younger African-Americans or in the presence of certain immunogenetic markers.

Key Words: CTLA-4 • effect modification • genetics • polymorphism • population-based • systemic lupus erythematosus

Lupus, Vol. 13, No. 10, 784-791 (2004)
DOI: 10.1191/0961203304lu1085oa


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