Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause well-known lung defects, but in the January issue of Gastroenterology, Chee Y. Ooi et al. describe specific CFTR genotypes that increase risk for pancreatitis.

Most patients with cystic fibrosis that carry mutations that severely disrupt CFTR function have a pancreatic insufficient (PI) phenotype. However, patients who carry a mutation on at least 1 allele that confers some residual ion channel function usually have sufficient exocrine pancreatic function to maintain normal nutrient digestion, without the use of pancreatic enzyme supplements.  Nonetheless, the prevalence of pancreatitis is high in these patients (22.4%)—it is a challenge to determine which of these patients are at greatest risk for pancreatitis.

Ooi et al. studied 277 patients with cystic fibrosis who did not have major pancreatic defects, although some had pancreatitis, and who had CFTR mutations on both alleles. The authors were able to predict and classify the functional severity of CFTR mutations based on a pancreatic insufficiency prevalence (PIP) score. Paradoxically, Ooi et al. found that genotypes associated with otherwise mild phenotypic effects have the greater risk for causing pancreatitis, compared with genotypes associated with moderate to severe disease phenotypes.  People with cystic fibrosis that have more residual CFTR function are therefore at greater risk for pancreatitis (see below figure).

The authors propose that patients with enough functional CFTR for the pancreas to function have an increased risk of pancreatitis, because sufficient pancreatic acinar tissue is present for obstructive ductal lesions to cause disease.

Pancreatitis is a strong risk factor for progressive decline in exocrine pancreatic function in people with cystic fibrosis. The findings of Ooi et al. provide insight into the complex pathogenesis of pancreatitis, and indicate the importance of monitoring exocrine pancreatic function and pancreatic sufficiency in these patients.

More Information on Cystic Fibrosis:

• The National Heart Lung and Blood Institute (NHLBI) Web site on Cystic Fibrosis
• Mayo Clinic Web site on Cystic Fibrosis
• Cystic Fibrosis Foundation

Read the article online:
Ooi CY, Dorfman R, Cipolli M, et al. Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis. Gastroenterology 2011;140:153–161.