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)-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.


CONCLUSIONS
CTLA-4 49A polymorphism and -318C/+49A/CT60G haplotype are associated with AIP in a Chinese population.
Chang
Ming-Chu
MC
Departments of Internal Medicine, Surgery, Radiology, Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Chang
Yu-Ting
YT
Tien
Yu-Wen
YW
Liang
Po-Chin
PC
Jan
I-Shiow
IS
Wei
Shu-Chen
SC
Wong
Jau-Min
JM
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics*; D060908:CTLA-4 Antigen; D002114:Calcinosis; D003460:Crystallization; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D014409:Tumor Necrosis Factor-alpha