The Prevalence of Cationic Trypsinogen (PRSS1) and Serine Protease Inhibitor, Kazal Type 1 (SPINK1) Gene Mutations in Polish Patients with Alcoholic and Idiopathic Chronic Pancreatitis

Background The main cause of chronic pancreatitis (CP) is excessive alcohol consumption. On the other hand, only 5–10% of heavy drinkers develop chronic pancreatitis. We have only limited information regarding the pathogenic mechanism by which alcohol leads to the disease. Mutations of the PRSS1 and SPINK 1 have been mostly implicated in hereditary and idiopathic CP, but their presence in other types of this disease have also been reported. Aims The aim of the study was to determine the frequency of PRSS1 and SPINK1 mutations in patients with chronic alcoholic (ACP) and idiopathic pancreatitis (ICP) as well as to investigate their relation to the clinical course of the disease. Methods The study included 33ACP and 14 ICP patients as well 46 healthy subjects. The diagnosis of CP was based on clinical data, ultrasound, and computed tomography. After isolation of DNA from peripheral blood two trypsinogen mutations were detected N29I and R122H by allelo-specific amplification polymerase chain reaction (ASA-PCR) and by the PCR-restriction fragment length polymorphism (RFLP). Beside this N34S mutation of SPINK1 was analyzed by PCR restriction fragment length polymorphism (PCR-RFLP). Results PRSS1 mutations have been detected in 11 (33%) patients with ACP. The frequency of the PRSS1 mutations was higher in patients with ACP than in controls (4.3%) (p\0.001). The frequency of PRSS1 mutation was present in 21.4% of ICP patients, which was significantly higher (p\0.05) than in controls. Overall, six (18%) SPINK1 mutations in ACP group have been detected. Among 14 patients with ICP, in four (28.6%) of them SPINK1 has been detected. The same mutations have also been found in three (6.5%) control subjects. The frequency of the N34S mutation was higher in patients with ICP than in the controls (p\ 0.05), but the frequency of N34S mutation did not differ between ACP and the control group. No relations have been detected between PRSS1 and SPINK1 mutations presence and clinical course and complications of CP. Conclusions Those preliminary data suggest the high prevalence of SPINK1 and PRSS1 mutations in the Polish population, generally, as well as in CP patients. It may be speculated that those mutations contribute to the development of chronic pancreatitis, especially in patients with alcohol overindulgence.