Mutations in the serine protease inhibitor kazal type 1 (SPINK1) gene in Japanese patients with pancreatitis

Recent studies have shown an association between the N34S mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene and chronic pancreatitis (CP). We here examined the prevalence of SPINK1 mutations in Japanese patients with pancreatitis.Genomic DNA was prepared from 80 Japanese patients with CP, 36 patients with acute pancreatitis (AP), and 165 healthy controls. All exons and the promotor region of the SPINK1 gene were amplified by the polymerase chain reaction, and directly sequenced.We found four types of mutation (N34S, IVS1-37T>C, -215G>A, and IVS3 + 2T>C) and two types of polymorphism (-253T>C and 272C>T). The N34S mutation cosegregated with IVS1-37T>C, and was present in 8 CP and 1 AP patients. The -215G>A mutation was in a complete linkage with IVS3 + 2T>C, and was present in 8 CP and 1 AP patients. The prevalences of [N34S; IVS1-37T>C] and [-215G>A; IVS3 + 2T>C] were significantly higher in patients with familial pancreatitis (38 and 13%, respectively) and with idiopathic CP (13 and 16%) than normal subjects (0.6 and 0%). In addition, the frequency of [N34S; IVS1-37T>C] mutation was higher in patients with autoimmune CP (33%).The SPINK1 gene mutations were associated with pancreatitis also in Japan.