Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis

Background & aims: Different mutations in the cystic fibrosis gene (CFTR) are associated with different functional status of the exocrine pancreas. We investigated whether CFTR genotypes determine the risk of pancreatitis in patients with cystic fibrosis (CF).

Methods: Patients with pancreatic-sufficient CF were identified from 2 CF population-based databases (N = 277; 62 with pancreatitis and 215 without pancreatitis); patients' genotypes and clinical characteristics were analyzed. The loss of pancreatic function associated with each CFTR genotype was determined based on the pancreatic insufficiency prevalence (PIP) score.

Results: Patients with pancreatitis were more likely to have genotypes associated with mild (70%) than moderate-severe (30%) PIP scores (P = .004). The cumulative proportion of patients who developed pancreatitis through to the age of 50 years was significantly greater for genotypes associated with mild (50%) than moderate-severe (27%) PIP scores (P = .006). The genotype associated with mild PIP scores had a hazard ratio of 2.4 for pancreatitis (95% confidence interval, 1.3-4.5; P = .006). Patients with pancreatitis were diagnosed with CF at an older median age than those without pancreatitis (14.9 years [interquartile range, 9.5-27.7] vs 9.3 years [interquartile range, 1.5-21.4]; P = .003) and had lower mean levels of sweat chloride than patients without pancreatitis (74.5 ± 26.2 mmol/L vs 82.8 ± 25.2 mmol/L; P = .03).

Conclusions: Specific CFTR genotypes are significantly associated with pancreatitis. Patients with genotypes associated with mild phenotypic effects have a greater risk of developing pancreatitis than patients with genotypes associated with moderate-severe phenotypes. This observation provides further insight into the complex pathogenesis of pancreatitis.