CTLA-4 gene polymorphism regulates CTLA-4 mRNA stability and protein level in patients with ulcerative colitis.
- Author:
Zhi-tao CHEN
1
,
2
;
Bing XIA
;
Ting JIANG
;
Feng ZHOU
;
Kai-fang ZOU
;
Liu-qing GE
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Antigens, CD; chemistry; genetics; metabolism; CTLA-4 Antigen; Case-Control Studies; Colitis, Ulcerative; genetics; metabolism; Female; Gene Expression Regulation; Genotype; Humans; Male; Phenotype; Polymorphism, Genetic; RNA Stability; genetics; RNA, Messenger; chemistry; genetics; metabolism; Solubility
- From: Chinese Journal of Medical Genetics 2010;27(6):603-609
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSflCTLA-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.
RESULTSAmong 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).
CONCLUSIONCTLA-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.