Schneider Alexander
Department of Medicine II (Gastroenterology, Hepatology and Infectious Diseases), University Hospital of Heidelberg at Mannheim, Theodor-Kutzer-Ufer 1-3 D-68135, Mannheim, Germany.
Gastroenterol Clin North Am. 2004 Dec;33(4):789-806. doi: 10.1016/j.gtc.2004.07.005.
In summary, SPINK1 is thought to play an important role in protecting the pancreas against excessive trypsinogen activation. SPINK1 mutations are associated with the development of acute and chronic pancreatitis and have been detected in all forms of chronic pancreatitis. The strong association of mutations in the PRSS1 gene and in the SPINK1 gene with chronic pancreatitis supports the concept of intracellular trypsin activation as an initiating and extremely important step in the development of pancreatitis. The N34S mutation represents the most frequently observed pancreatitis-associated SPINK1 variant. Because the SPINK1 N34S mutation is very common in the general population, it is unlikely that this mutation alone can initiate the development of chronic pancreatitis. Thus, it rather appears that in most patients with SPINK1-associated chronic pancreatitis, this genetic variant acts as disease modifier or within a polygenic model with other yet unidentified genes or environmental cofactors. The possible interaction of mutations in the SPINK1 gene with other pancreatitis-associated susceptibility genes has to be investigated in future research efforts. The most promising candidate gene for such an interaction is the CFTR gene, because genetic alterations within the CFTR gene are also common in the general population and already have been associated with chronic pancreatitis.
总之，丝氨酸蛋白酶抑制剂Kazal型1（SPINK1）被认为在保护胰腺免受过多胰蛋白酶原激活方面发挥重要作用。SPINK1突变与急性和慢性胰腺炎的发生相关，且在所有形式的慢性胰腺炎中均已被检测到。PRSS1基因和SPINK1基因中的突变与慢性胰腺炎的强关联支持了细胞内胰蛋白酶激活是胰腺炎发生过程中起始且极为重要步骤的概念。N34S突变是最常观察到的与胰腺炎相关的SPINK1变异体。由于SPINK1 N34S突变在普通人群中非常常见，仅这一突变不太可能引发慢性胰腺炎的发生。因此，在大多数与SPINK1相关的慢性胰腺炎患者中，这种基因变异似乎更像是疾病修饰因子，或在与其他尚未明确的基因或环境协同因子组成的多基因模型中发挥作用。未来的研究工作必须对SPINK1基因中的突变与其他胰腺炎相关易感基因之间可能的相互作用进行研究。这种相互作用最有前景的候选基因是囊性纤维化跨膜传导调节因子（CFTR）基因，因为CFTR基因内的遗传改变在普通人群中也很常见，且已与慢性胰腺炎相关。
