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Clinical Chemistry 53: 1700-1705, 2007; 10.1373/clinchem.2007.085951
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(Clinical Chemistry. 2007;53:1700-1705.)
© 2007 American Association for Clinical Chemistry, Inc.

Clinical Immunology

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

Ming-Chu Chang1, Yu-Ting Chang1, Yu-Wen Tien2, Po-Chin Liang3, I-Shiow Jan4, Shu-Chen Wei1 and Jau-Min Wong1,a

Departments of1 Internal Medicine, 2 Surgery, 3 Radiology, and 4 Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.

aAddress correspondence to this author at: Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung Shan South Rd., Taipei, Taiwan. Fax 886-2-23947927; e-mail jmwong{at}ha.mc.ntu.edu.tw.

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)-{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.

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-{alpha} 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.






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