Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis.
BACKGROUND
The pancreas is one of the primary organs affected by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. While exocrine pancreatic insufficiency is a well-recognized complication of cystic fibrosis (CF), symptomatic pancreatitis is often under-recognized.


RESULTS
The aim of this review is to provide a general overview of CFTR mutation-associated pancreatitis, which affects patients with pancreatic sufficient CF, CFTR-related pancreatitis, and idiopathic pancreatitis. The current hypothesis regarding the role of CFTR dysfunction in the pathogenesis of pancreatitis, and concepts on genotype-phenotype correlations between CFTR and symptomatic pancreatitis will be reviewed. Symptomatic pancreatitis occurs in 20% of pancreatic sufficient CF patients. In order to evaluate genotype-phenotype correlations, the Pancreatic Insufficiency Prevalence (PIP) score was developed and validated to determine severity in a large number of CFTR mutations. Specific CFTR genotypes are significantly associated with pancreatitis. Patients who carry genotypes with mild phenotypic effects have a greater risk of developing pancreatitis than patients carrying genotypes with moderate-severe phenotypic consequences at any given time.


CONCLUSIONS
The genotype-phenotype correlation in pancreatitis is unique compared to other organ manifestations but still consistent with the complex monogenic nature of CF. Paradoxically, genotypes associated with otherwise mild phenotypic effects have a greater risk for causing pancreatitis; compared with genotypes associated with moderate to severe disease phenotypes. Greater understanding into the underlying mechanisms of disease is much needed. The emergence of CFTR-assist therapies may potentially play a future role in the treatment of CFTR-mutation associated pancreatitis.
School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia. keith.ooi@unsw.edu.au
Chee Y
CY
Ooi
Peter R
PR
Durie
D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004067:Digestive System Neoplasms / Q000209:etiology; D010188:Exocrine Pancreatic Insufficiency / Q000209:etiology / Q000503:physiopathology; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D009154:Mutation; D010179:Pancreas / Q000473:pathology / Q000503:physiopathology; D010195:Pancreatitis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index
D019005:Cystic Fibrosis Transmembrane Conductance Regulator