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.
OBJECTIVE
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.
Department of Gastroenterology, Wuhan University Zhongnan Hospital, Clinical Research Center for Intestinal & Colorectal Diseases of Hubei Province, Wuhan, China.
Zhitao
Z
Chen
Feng
F
Zhou
Sha
S
Huang
Ting
T
Jiang
Liping
L
Chen
Liuqing
L
Ge
Bing
B
Xia
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015703:Antigens, CD / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D003424:Crohn Disease / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D055815:Young Adult
D015703:Antigens, CD; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D002097:C-Reactive Protein