Fujibayashi Shugo, Sasajima Junpei, Goto Takuma, Tanaka Hiroki, Kawabata Hidemasa, Fujii Tsuneshi, Nakamura Kazumasa, Chiba Atsushi, Yanagawa Nobuyuki, Moriichi Kentaro, Fujiya Mikihiro, Kohgo Yutaka
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Hokkaido, Japan.
Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, 1-1-1-1 Akebono, Asahikawa 070-8530, Hokkaido, Japan.
Biochem Biophys Rep. 2016 Mar 24;6:76-81. doi: 10.1016/j.bbrep.2016.03.005. eCollection 2016 Jul.
The pathogenesis of autoimmune pancreatitis is unknown. In the present study we used high-throughput sequencing with next generation sequencing to identify the candidate genes associated with AIP. A total of 27 type 1 AIP patients and 30 healthy blood donors were recruited, and DNA samples were isolated from their mononuclear cells. A high-throughput sequencer with an original custom panel of 1031 genes was used to detect the genetic variants in each sample. Polymorphisms of CACNA1S (c.4642C>T), rs41554316, rs2231119, rs1042131, rs2838171, P2RX3 (c.195delG), rs75639061, SMAD7 (c.624delC) and TOP1 (c.2007delG), were identified as candidate genetic variants in patients with type 1 AIP. P2RX3 and TOP1 were significantly associated with AIP, even after adjusting bay means of Bonferroni's correction. In addition, we also identified eight candidate genetic variants that were associated with the relapse of type 1 AIP, namely: rs1143146, rs1050716, HLA-C (c.759_763delCCCCCinsTCCCG), rs1050451, rs4154112, rs1049069, CACNA1C (c.5996delC) and CXCR3 (c.630_631delGC). Finally polymorphisms of rs1050716 and rs111493987 were identified as candidate genetic variants associated with extra-pancreatic lesions in patients with type 1 AIP. These candidates might be used as markers of AIP susceptibility and could contribute to the pathogenesis of type 1 AIP.
自身免疫性胰腺炎的发病机制尚不清楚。在本研究中，我们使用新一代测序的高通量测序技术来鉴定与1型自身免疫性胰腺炎（AIP）相关的候选基因。共招募了27例1型AIP患者和30名健康献血者，并从他们的单核细胞中分离出DNA样本。使用具有1031个基因的原始定制面板的高通量测序仪来检测每个样本中的基因变异。CACNA1S（c.4642C>T）、rs41554316、rs2231119、rs1042131、rs2838171、P2RX3（c.195delG）、rs75639061、SMAD7（c.624delC）和TOP1（c.2007delG）的多态性被鉴定为1型AIP患者的候选基因变异。即使在经Bonferroni校正的贝叶斯均值调整后，P2RX3和TOP1仍与AIP显著相关。此外，我们还鉴定出8个与1型AIP复发相关的候选基因变异，即：rs1143146、rs1050716、HLA-C（c.759_763delCCCCCinsTCCCG）、rs1050451、rs4154112、rs1049069、CACNA1C（c.5996delC）和CXCR3（c.630_631delGC）。最后，rs1050716和rs111493987的多态性被鉴定为与1型AIP患者胰腺外病变相关的候选基因变异。这些候选基因可能用作AIP易感性的标志物，并可能有助于1型AIP的发病机制研究。
