Different CFTR mutational spectrum in alcoholic and idiopathic chronic pancreatitis?
OBJECTIVE
Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are responsible for cystic fibrosis (CF) and have been postulated as a predisposing risk factor to chronic pancreatitis (CP), but controversial results demand additional support. We have therefore investigated the role of the CFTR gene in a cohort of 68 CP patients.


METHODS
We have performed the CFTR gene analysis using 2 screening techniques. Fragments showing abnormal migration patterns were characterized by sequencing. Patients were classified in alcoholic (ACP) (n = 37) and idiopathic (ICP) (n = 31) chronic pancreatitis. Clinical features of CP and CF were evaluated.


RESULTS
Sixteen mutations/variants were identified in 27 patients (40%), most of them (35%) presenting a single CFTR mutant gene. The 1716G/A variant showed the highest frequency accounting for 22% in ICP and 5% in ACP, in contrast with other more common mutations such as F508del found in 8% of ACP and the 5T variant identified in 7% of patients. Acute pancreatitis, abdominal pain, tobacco, pancreatic calcifications, and pancreatic pseudocysts showed significant higher values in ACP than ICP patients. No significant differences were found between patients with and without CFTR mutations.


CONCLUSIONS
Apart from reinforcing previous findings our data highlight the increased susceptibility of CFTR heterozygous to developing CP. Heterozygosity, combined with other factors, places these individuals at greater risk.
Casals
Teresa
T
Medical and Molecular Genetics Center-IRO, Hospital DIR, Barcelona, Spain. tcasals@iro.es
Aparisi
Luís
L
Martínez-Costa
Cecilia
C
Giménez
Javier
J
Ramos
Maria D
MD
Mora
Josefina
J
Diaz
Juan
J
Boadas
Jaume
J
Estivill
Xavier
X
Farré
Antoni
A
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010195:Pancreatitis / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D019512:Pancreatitis, Alcoholic / Q000235:genetics*
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator