Polymorphism in the KCNA3 gene is associated with susceptibility to autoimmune pancreatitis in the Japanese population.
Polymorphism in the KCNA3 gene is associated with susceptibility to autoimmune pancreatitis in the Japanese population.
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DOI：
10.3233/dma-2011-0820
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Kawa S
中科院分区：
文献类型：
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作者：
Ota M;Ito T;Umemura T;Katsuyama Y;Yoshizawa K;Hamano H;Kawa S
自身免疫性胰腺炎（AIP）的特征是主胰管不规则狭窄、胰腺肿胀和高血清免疫球蛋白G4引起的淋巴浆细胞性炎症的组织学证据，与普通胰腺炎不同。然而，涉及AIP的病因学和病理生理学的遗传因素仍不清楚。64例自身免疫性胰腺炎患者（53例男性，11例女性;平均年龄62.4岁）和104例日本健康对照者入组本研究。我们进行了关联分析，使用400个微卫星标记的平均间距为10.8厘米的基因组。我们还评估了AIP与钾电压门控通道，Shaker相关亚家族，成员3基因（KCNA 3）周围20 kb区域内的7个单核苷酸多态性（SNP）的相关性。我们发现了6个与易感性相关的具有统计学意义的标记物（D1 S2726、D5 S410、D 6S 460、D10 S548、D15 S128和D20 S186; P < 0.05）。显示强关联的周围区域（P = 7.4 × 10−7，Pc = 0.0015）包含KCNA 3基因。KCNA 3基因SNP分型结果显示，4个SNP位点（rs 2840381、rs 1058184、rs 2640480、rs 1319782）与AIP易感性显著相关（P < 0.007）。已知KCNA 3参与自身反应性效应和记忆T细胞介导的自身免疫性疾病的免疫调节。我们的研究结果提供了KCNA 3与AIP相关的第一个证据，并表明KCNA 3可能影响AIP的风险。
Autoimmune pancreatitis (AIP), characterized by irregular narrowing of the main pancreatic duct, swelling of the pancreas, and histological evidence of lymphoplasmacytic inflammation by high serum immunoglobulin G4, is distinct from ordinary pancreatitis. However, genetic factors involved in the etiology and pathophysiology of AIP remain unclear. Sixty-four patients with autoimmune pancreatitis (53 men, 11 women; mean age, 62.4 years) and 104 healthy Japanese controls were enrolled in this study. We performed an association analysis using 400 microsatellite markers with an average spacing of 10.8 cM in the genome. We also evaluated the association of AIP with seven single nucleotide polymorphisms (SNPs) within the 20-kb region around the potassium voltage-gated channel, shaker-related subfamily, member 3 gene (KCNA3). We identified six statistically significant markers (D1S2726, D5S410, D6S460, D10S548, D15S128, and D20S186; P < 0.05) related to susceptibility. The surrounding region showing the strong association (P = 7.4 × 10−7, Pc = 0.0015) contained the KCNA3 gene. Further analysis by SNP genotyping in KCNA3 gene revealed that four SNPs (rs2840381, rs1058184, rs2640480, rs1319782) were significantly associated with the AIP susceptibility (P < 0.007). KCNA3 is known to be involved in immunomodulation of autoreactive effector and memory T cell–mediated autoimmune diseases. Our findings provide the first evidence that KCNA3 is associated with AIP and suggest that KCNA3 may influence the risk for AIP.