title: [CTLA-4 gene polymorphism regulates CTLA-4 mRNA stability and protein level in patients with ulcerative colitis].
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Wuhan University Zhongnan Hospital; Clinical Research Center for Intestinal & Colorectal Diseases of Hubei Province and Key Laboratory of Allergy and Immune-related Diseases, Wuhan, Hubei, P.R. China.
authors.forename: Zhi-tao
authors.initials: ZT
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Ting
authors.initials: T
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Kai-fang
authors.initials: KF
authors.lastname: Zou
authors.forename: Liu-qing
authors.initials: LQ
authors.lastname: Ge
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012995:Solubility
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D012333:RNA, Messenger