Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis.
BACKGROUND
The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP).


METHODS
A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed.


RESULTS
Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (-1 mV, p < 0.0001) and pancreatic insufficient (-3 mV, p < 0.0001) patients.


CONCLUSIONS
These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis.
Division of Gastroenterology and Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Andres
A
Gelrud
Sunil
S
Sheth
Subhas
S
Banerjee
Deborah
D
Weed
Julie
J
Shea
Ram
R
Chuttani
Douglas A
DA
Howell
Jennifer J
JJ
Telford
David L
DL
Carr-Locke
Meredith M
MM
Regan
Lynda
L
Ellis
Peter R
PR
Durie
Steven D
SD
Freedman
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018118:Chloride Channels / Q000378:metabolism; D003550:Cystic Fibrosis / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D017136:Ion Transport; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D008875:Middle Aged; D009154:Mutation; D009297:Nasal Mucosa / Q000503:physiopathology; D010179:Pancreas / Q000002:abnormalities*; D010195:Pancreatitis / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D012008:Recurrence; D012964:Sodium / Q000378:metabolism
C505032:CFTR protein, human; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium; D007545:Isoproterenol