SPINK1 gene mutations and pancreatitis in Japan
SPINK1 gene mutations and pancreatitis in Japan
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DOI：
10.1111/j.1440-1746.2006.04594.x
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发表时间：
2006-10-01
影响因子：
4.1
通讯作者：
Masamune, Atsushi
中科院分区：
文献类型：
--
作者：
Shimosegawa, Tooru;Kume, Kiyoshi;Masamune, Atsushi
SPINK1可以抑制高达20%的胰酶活性，可能是保护胰腺免受自身消化的一个主要机制。2000年，Witt et al.日本首次认识到SPINK1基因突变与慢性胰腺炎(CP)之间的关联，但SPINK1基因突变在胰腺炎中的意义及其与饮酒的关系在日本仍不清楚。本研究旨在阐明日本不同病因CP患者中SPINK1基因突变的发生率，并探讨酒精代谢与乙醇脱氢酶(ADH)和乙醛脱氢酶-2(ALDH2)等关键酶基因多态性的关系。应用聚合酶链式反应-限制性片段长度多态性和直接测序法对156例CP患者和165例健康志愿者的SPINK1基因突变进行了检测。在日本，特发性CP患者[N34S；IVS1-37T>；C]和[-215G>；A；IVS3+2T>；C]的患病率(分别为10.6%和12.8%)显著高于正常人(0.6%和0%)。日本人群中[-215G>；A；IVS3+2T>；C]突变频率显著高于其他人群。在酒精性CP中，[-215G>；A；IVS3+2T>；C]突变仅见于少数患者(3.9%)。ADH2和ALDH2基因多态性分析发现ADH2*2等位基因与酒精性CP相关，且ADH2*2/2*2等位基因有增加胰腺假性囊肿发病风险的趋势。总之，在日本，SPINK1基因的[-215G>；A；IVS3+2T>；C]突变可能形成了胰腺炎的独特遗传背景。
SPINK1 can inhibit up to 20% of trypsin activity, and may constitute one major mechanism to protect the pancreas from autodigestion. In 2000, Witt et al. first recognized the association between mutations in the SPINK1 gene and chronic pancreatitis (CP), but the significance of SPINK1 gene mutation in pancreatitis and its relation to alcohol consumption remains unclear in Japan. The aim of the present paper was to clarify the incidence of SPINK1 mutations in CP patients with various etiologies in Japan and, in addition, to examine the relationship between alcohol metabolism and the polymorphisms in the key enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase-2 (ALDH2). A total of 156 patients with CP, and 165 healthy volunteers, all Japanese, were examined for the SPINK1 mutations by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. In Japan, the prevalence of [N34S; IVS1-37T > C] and [-215G > A; IVS3 + 2T > C] was significantly higher in patients with idiopathic CP (10.6% and 12.8%, respectively) than normal subjects (0.6% and 0%). The frequency of the [-215G > A; IVS3 + 2T > C] mutation in Japan was significantly higher than that reported in other populations. Concerning alcoholic CP, the [-215G > A; IVS3 + 2T > C] mutation was found in only a small number of patients (3.9%). On analysis of ADH2 and ALDH2 gene polymorphisms an association was found between ADH2*2 allele and alcoholic CP, and the ADH2*2/2*2 genotype had a tendency to increase the risk of developing pancreatic pseudocyst. In conclusion, in Japan the [-215G > A; IVS3 + 2T > C] mutation in the SPINK1 gene may form a unique genetic background for pancreatitis.