T-Cell Regulatory Gene CTLA-4 Polymorphism/Haplotype Association with Autoimmune Pancreatitis

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 53; no. 9; pp. 1700 - 1705
• Main Authors: Chang, Ming-Chu, Chang, Yu-Ting, Tien, Yu-Wen, Liang, Po-Chin, Jan, I-Shiow, Wei, Shu-Chen, Wong, Jau-Min
• Format: Journal Article
• Language: English
• Published: Washington, DC Am Assoc Clin Chem 01.09.2007; American Association for Clinical Chemistry; Oxford University Press
• Subjects: Adult; Aged; Analytical, structural and metabolic biochemistry; Antigens, CD - genetics; Antigens, Differentiation - genetics; Asian Continental Ancestry Group; Autoimmune diseases; Autoimmune Diseases - ethnology; Autoimmune Diseases - genetics; Biological and medical sciences; Calcinosis; Cells; Crystallization; CTLA-4 Antigen; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genes; Genetic Predisposition to Disease; Genotype; Haplotypes; Heterozygote; Humans; Immune response; Investigative techniques, diagnostic techniques (general aspects); Lymphocytes; Male; Medical sciences; Middle Aged; Pancreas; Pancreatitis, Chronic - ethnology; Pancreatitis, Chronic - genetics; Pancreatitis, Chronic - pathology; Polymerase Chain Reaction; Promoter Regions, Genetic; Prospective Studies; Studies; Tumor Necrosis Factor-alpha - genetics; Autoimmunity; Genetic variability; Pancreatitis; Genotype; Biochemistry; Cytotoxic T lymphocyte antigen 4; Association; Clinical biology; T-Lymphocyte; Digestive diseases; Molecular biology; Haplotype; Regulatory cell; Pancreatic disease
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2007.085951

Autoimmune pancreatitis (AIP) is a distinct disease entity of chronic pancreatitis. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a key negative regulator of the T-cell immune response, and its gene is highly polymorphic. Many positive associations between cytotoxic T-lymphocyte-associated protein 4 (CTLA4) single-nucleotide polymorphisms and various autoimmune diseases have been identified. We investigated possible genetic associations of CTLA4 in a Chinese population with AIP. We performed genotyping for CTLA4 (49 A/G, -318 C/T, and CT60 A/G) and tumor necrosis factor (TNF)-alpha promoter (-857 C/T, -863 C/A, and -1031 C/T) by use of PCR sequence-specific primers and direct sequencing, respectively, in 46 patients with AIP, 78 patients with chronic calcifying pancreatitis (CCP), and 200 healthy individuals. We found a significant increase in CTLA4 49A carriers in patients with AIP compared with healthy individuals (78.3% vs 48%; P <0.0001). The frequency of CTLA4 49A was also significantly higher in patients with AIP compared with CCP (78.3% vs 37.1%; P <0.0001). CTLA4 49A conferred a higher risk of AIP [with CCP, odds ratio (OR) 7.20; P <0.0001]. The -318C/+49A/CT60G haplotype was associated with a higher susceptibility to AIP (OR 8.53; P = 0.001). The TNF-alpha promoter -863A was associated with extrapancreatic involvement in patients with AIP. CTLA-4 49A polymorphism and -318C/+49A/CT60G haplotype are associated with AIP in a Chinese population.