T-Cell regulatory gene CTLA-4 Polymorphism/Haplotype association with autoimmune pancreatitis

T-Cell regulatory gene CTLA-4 Polymorphism/Haplotype association with autoimmune pancreatitis
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DOI:
10.1373/clinchem.2007.085951
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发表时间:
2007-09-01
期刊:
影响因子:
9.3
通讯作者:
Wong, Jau-Min
Wong, Jau-Min
中科院分区:
医学1区
文献类型:
--
作者:
Chang, Ming-Chu;Chang, Yu-Ting;Wong, Jau-Min

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背景:自身免疫性胰腺炎(AIP)是一种独特的慢性胰腺炎疾病。细胞毒性T淋巴细胞相关抗原4 (CTLA-4)是T细胞免疫应答的关键负调控因子,其基因具有高度多态性。细胞毒性t淋巴细胞相关蛋白4 (CTLA4)单核苷酸多态性与各种自身免疫性疾病之间存在许多正相关。我们调查了中国AlP人群中CTLA4可能的遗传关联。方法:对46例AIP患者、78例慢性钙化性胰腺炎(CCP)患者和200例健康人分别采用PCR序列特异性引物和直接测序对CTLA4 (49 A/G、-318 C/T和CT60 A/G)和肿瘤坏死因子(TNF)- α启动子(-857 C/T、-863 C/A和-1031 C/T)进行基因分型。结果:我们发现AIP患者的CTLA4 49A携带者与健康人相比显著增加(78.3% vs 48%; P < 0.0001)。AIP患者CTLA4 49A的频率也明显高于CCP患者(78.3% vs 37.1%
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 AlP.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