The prevalence of mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene in idiopathic chronic pancreatitis has been shown to be increased. The aim of this study was to prospectively analyze the frequency of such mutations in a homogeneous group of patients with idiopathic pancreatitis studied in a French Gastroenterology department.
Patients and methods: Between April 1999 and December 2001, all patients with unexplained chronic or recurrent acute pancreatitis were studied. Other causes of pancreatitis were excluded and no patient had personal signs or family history compatible with cystic fibrosis. Following informed written consent, genetic analysis for CFTR was performed using an oligonucleotid ligation assay, on the 31 most frequently known mutations of the CFTR gene. A complementary analysis for variants in exons 9, 10 and 17a, thought to be implicated in atypical cystic fibrosis, was also performed using denaturing gradient gel electrophoresis.
Results: Idiopathic pancreatitis occurred in 64 patients (chronic, n=30; recurrent acute, n=34) with a median age of 36 years. Eighteen CFTR mutations or variants were detected in 16 patients (25%): DeltaF508 (n=7), L997F (n=2), E528E (n=4), 5T (n=5). Two patients were compound heterozygous. The frequency of DeltaF508 mutations was greater than that of the general population (10.9 vs 2.4%; P<0.001). Pancreatitis was diagnosed at a median age of 32 years in mutation-positive patients compared to 39 in mutation-negative patients. The prevalence of CFTR mutations was 35.5% in patients < or =35 years against 15.1% in those > 35 years (P=0.06). The clinical course of pancreatitis (severity and complication rates) was not altered by the presence of a mutation.
Conclusion: One-quarter of all patients and one-third of those < or =35 years with idiopathic pancreatitis have at least one mutation of the CFTR gene. The presence of a CFTR mutation appears to predict the development of pancreatitis at an earlier age.