Genetic predisposition to alcoholic chronic pancreatitis.
The mechanisms leading to alcoholic chronic pancreatitis in humans have remained elusive. Numerous questions surround the apparent random nature of the disease in which 1 person is hit with alcoholic chronic pancreatitis while the next is spared. Why do fewer than 10% of chronic, heavy alcohol users ever develop pancreatitis, while others develop alcoholic liver disease, neuropathy, or other alcohol-associated problems? Why do laboratory animals, fed large amounts of alcohol for prolonged periods of time, fail to develop typical chronic pancreatitis? Why are heavy alcohol users from a black African background more likely to develop pancreatic diseases than Caucasians, whereas the opposite is true for the development of liver disease? The answers underlying these questions appear to reflect the differences in underlying genetic susceptibility, environmental exposure, and the interaction between these factors. Thus, even cases of "typical" alcoholic chronic pancreatitis or other forms of pancreatitis appear to be complex diseases. Recently, several genetic mutations have been identified that increase the susceptibility to pancreatitis. However, the major common gene mutations in CFTR, PRSS1, and SPINK1 only slightly increase the risk of alcoholic chronic pancreatitis. New genetic, environmental, and triggering factors must be considered to gain further insight into the mechanisms leading to alcoholic chronic pancreatitis so that strategies for treatment and prevention can be developed.
Whitcomb
David C
DC
Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, and the VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania, USA. whitcomb@pitt.edu
D000428:Alcohol Drinking / Q000009:adverse effects; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D019512:Pancreatitis, Alcoholic / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics; D014362:Trypsinogen / Q000235:genetics
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin