Background: Risk factors for chronic pancreatitis (CP) are largely unknown except for alcohol. Identification of environmental and genetic risk factors is important for the early diagnosis of CP. We here examined the prevalence of the serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in Japanese patients with CP, and whether the disease course was different between mutation-positive and -negative patients.
Methods: Genomic DNA was prepared from 96 CP patients and 165 healthy controls. All exons and the promoter region of the SPINK1 gene were amplified by polymerase chain reaction, and directly sequenced. Clinical courses of the patients were reviewed.
Results: The prevalence of [N34S; IVS1-37T>C] and [-215G>A; IVS3+2T>C] mutations was higher in patients with familial (55.6% and 11.1%, respectively) and idiopathic (15.2% and 18.1%) CP than in controls (0.6% and 0%). The N34S and IVS3+2T>C mutations were present in 0% and 4.5% (P<0.05 vs control) of patients with alcoholic CP. Patients with the N34S mutation presented with earlier symptom onset and more dilatation of the main pancreatic duct, followed by more frequent surgical and/or endoscopic intervention and pancreatic cancer development than those without SPINK1 mutations.
Conclusions: SPINK1 mutations were associated with idiopathic and familial CP, whereas the contribution was less evident in alcoholic CP. Patients with the N34S mutation presented more severe clinical courses, implying that genetic risk assessment might be useful to identify individuals who are likely to develop severe CP, and allow targeted attention to slow or prevent disease progression.