T-cell regulatory gene CTLA-4 polymorphism/haplotype association with autoimmune pancreatitis

Background: 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. Methods: We performed genotyping for CTLA4 (49 A/G, -318 C/T, and CT60 A/G) and tumor necrosis factor (TNF)-α 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. Results: 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-α promoter -863A was associated with extrapancreatic involvement in patients with AIP. Conclusion: CTLA-4 49A polymorphism and -318C/+49A/CT60G haplotype are associated with AIP in a Chinese population. ? 2007 American Association for Clinical Chemistry.