CTLA-4 gene polymorphism regulates CTLA-4 mRNA stability and protein level in patients with ulcerative colitis / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 603-609, 2010.
Article
in Chinese
| WPRIM
| ID: wpr-234354
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of (AT)n repeat polymorphism of the 3'untranslated region in cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene on CTLA-4 mRNA stability and full length (flCTLA-4) and soluble CTLA4 (sCTLA-4) expression in ulcerative colitis (UC).</p><p><b>METHODS</b>flCTLA-4 mRNA in colonic biopsies and sCTLA-4 mRNA stability in peripheral blood mononuclear cells of UC patients were measured by quantitative PCR and half-life, respectively. The protein expression of flCTLA-4 in colonic biopsies and sCTLA-4 in sera of UC patients were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The polymorphism of CTLA-4 (AT)n repeats in 300 UC and 700 age and sex matched healthy controls was genotyped by fluorescent PCR.</p><p><b>RESULTS</b>Among the UC patients, sCTLA-4 mRNA expression levels were decreased in active disease compared to non-active disease (P= 0.004). Carriers of the longer alleles of the (AT)n repeats expressed lower levels of flCTLA-4 and sCTLA-4 mRNA and sCTLA-4 protein than those of the shorter alleles in UC (all P< 0.01), and mRNA with long (AT)n repeat alleles has shorter half-life than mRNA with short alleles and, hence, are unstable. The frequency of long allele carriers of CTLA-4 (AT)n repeats was significantly higher in UC patients than in the healthy controls (22.0% vs. 6.3%, P< 0.01, OR= 4.21, 95% CI 2.79-6.33), and associated with extensive colitis (P= 0.008).</p><p><b>CONCLUSION</b>CTLA-4 gene expression levels were associated with (AT)n repeat polymorphisms in UC patients. The expression of CTLA-4 mRNA and protein were decreased in carriers of the longer alleles of the (AT)n repeats of CTLA-4 gene. This study suggests that CTLA-4 plays an important role in genetic risk and pathophysiology for UC in central China.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phenotype
/
Polymorphism, Genetic
/
Solubility
/
RNA, Messenger
/
Colitis, Ulcerative
/
Antigens, CD
/
Case-Control Studies
/
Chemistry
/
Gene Expression Regulation
/
RNA Stability
Type of study:
Observational study
/
Risk factors
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
Chinese
Journal:
Chinese Journal of Medical Genetics
Year:
2010
Type:
Article
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