Association of cytotoxic T lymphocyte associated antigen-4 gene (rs60872763) polymorphism with Crohn's disease and high levels of serum sCTLA-4 in Crohn's disease

J Gastroenterol Hepatol. 2011 May;26(5):924-30. doi: 10.1111/j.1440-1746.2011.06662.x.

Abstract

Background and aim: Our aim was to evaluate cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphisms in Crohn's disease (CD) and explore soluble CTLA-4 (sCTLA-4) levels in serum of CD patients in central China.

Methods: A total of 126 Chinese CD patients and 300 healthy controls were enrolled in this study. CTLA-4 (AT)n repeat polymorphism was genotyped by a semiautomatic fluorescently labeled polymerase chain reaction (PCR) method, and CTLA-4 -1661A/G and -1722T/C polymorphisms were genotyped by DNA sequencing. Serum sCTLA-4 and C-reactive protein (CRP) levels were determined by enzyme linked immunosorbent assay (ELISA) and immunonephelometry, respectively.

Results: The frequency of 84 bp allele of CTLA-4 (AT)n repeats was lower in CD patients than in the healthy controls (22.2% vs 33.2%, P = 0.001, odds ratio = 0.58, 95% confidence interval: 0.41-0.81). The 84 bp allele carriers of (AT)n repeats were associated with non-stricturing and non-penetrating disease behavior in CD patients (P = 0.007). Serum sCTLA-4 levels were more elevated in CD patients than in the healthy controls (P < 0.001). Among CD patients, serum sCTLA-4 levels were increased in active disease compared with inactive disease (P = 0.015), and were correlated with CRP levels (r = 0.524, P < 0.001). Serum sCTLA-4 levels were higher in CD patients with stricturing disease behavior than in patients with other disease behaviors (P = 0.009).

Conclusions: 84 bp allele of CTLA-4 (AT)n repeat polymorphism was associated with CD in central China. sCTLA-4 levels were highly expressed in CD, especially in active disease, and were correlated with CRP levels and disease behavior in CD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Antigens, CD / blood*
  • Antigens, CD / genetics*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • CTLA-4 Antigen
  • Case-Control Studies
  • Chi-Square Distribution
  • China
  • Crohn Disease / blood
  • Crohn Disease / genetics*
  • Crohn Disease / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Nephelometry and Turbidimetry
  • Odds Ratio
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Up-Regulation
  • Young Adult

Substances

  • Antigens, CD
  • Biomarkers
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • C-Reactive Protein