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Genes Immun. 2010 Oct;11(7):573-83. doi: 10.1038/gene.2010.16. Epub 2010 May 6.

CTLA4 -1661A/G and 3'UTR long repeat polymorphisms are associated with ulcerative colitis and influence CTLA4 mRNA and protein expression.

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Department of Gastroenterology, Wuhan University Zhongnan Hospital, PR China.


Reduced cytotoxic T-lymphocyte antigen 4 (CTLA4) expression has been proposed as a risk for autoimmunity. CTLA4 polymorphisms have been associated with several autoimmune diseases, including ulcerative colitis (UC). In this study, we performed genotyping for CTLA4 -1661A/G, -1722T/C and 3' untranslated region (AT)n repeat polymorphisms in 300 Chinese UC patients and in 700 healthy controls, and evaluated the effects of polymorphisms on full-length (flCTLA4) and soluble CTLA4 (sCTLA4) expression in UC patients. The frequency of the -1661G allele was higher in UC patients than in healthy controls (16.5 vs 11.4%, P=0.003, odds ratio (OR)=1.53, 95% confidence interval (95% CI): 1.17-2.01). The prevalence of (AT)n repeats of the CTLA4 gene carrying long alleles (≥116 bp) was more common in UC patients than in healthy controls (22.0 vs 6.3%, P<0.001, OR=4.21, 95% CI: 2.79-6.33), and was associated with extensive colitis (P=0.008). Among UC patients, long-allele carriers expressed lower levels of flCTLA4 and sCTLA4 mRNA and sCTLA4 protein than did short-allele carriers (P<0.001, P<0.001, P<0.001, respectively). CTLA4 gene -1661A/G and long 3' untranslated region (AT)n repeat polymorphisms are associated with UC in Central China. This is likely from decreased expressions of sCTLA4 mRNA and sCTLA4 protein. Our study suggests that CTLA4 has an important role in susceptibility for UC in Central China.

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