Analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene mutations in Japanese patients with chronic pancreatitis

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. Several studies have demonstrated that mutations in the c ationic trypsinogen (PRSS1) gene and the cystic fibrosis transmembrane cond uctance regulator (CFTR) gene are causative of the pathogenesis in a subset of hereditary and/or idiopathic CP cases. Recently, the N34S alteration of the pancreatic secretory trypsin inhibitor (PSTI) gene has been suggested to be closely associated with the pathogenesis of hereditary and/or idiopat hic CP. Herein we analyzed genetic alterations of the PSTI gene in 32 unrel ated Japanese CP patients who developed juvenile-onset CP or had a family h istory of CP, 5 patients were found to harbor alterations in this gene. In 3 of these 5 patients, heterozygous N34S alterations were found; this frequ ency is significantly lower than that in Caucasian patients reported previo usly. Moreover, a novel homozygous G-to-A transition in the promoter region of PSTI at 215bp upstream from the translation initiation site (--215G>A) was observed in 2 patients. We further surveyed the -215G>A alteration in 1 17 normal individuals; none of these individuals harbored this alteration. Our results suggested that the -215G>A alteration, as well as the N34S alte ration. is a predisposing factor for CP.