期刊
LUPUS
卷 13, 期 10, 页码 784-791出版社
ARNOLD, HODDER HEADLINE PLC
DOI: 10.1191/0961203304lu1085oa
关键词
CTLA-4; effect modification; genetics; polymorphism; population-based; systemic lupus erythematosus
类别
资金
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [Z01ES049023] Funding Source: NIH RePORTER
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 (-1722T/C, -1661A/G, -318C/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 -1661G allele, yielding a significant positive association with SLE in younger (less than or equal to 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.
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