Genetic polymorphisms in alcoholic pancreatitis.
BACKGROUND
Chronic, excessive alcohol consumption is clearly associated with acute and chronic pancreatitis. However, both clinical and laboratory studies demonstrate that alcohol consumption alone does not directly cause alcoholic chronic pancreatitis. Growing evidence suggests that environmental and possibly genetic cofactors must also be present to overcome the redundant mechanisms protecting the pancreas from pancreatitis and facilitating complete recovery.


METHODS
The SAPE hypothesis model was used to organize potential triggering factors, susceptibility factors and disease-modifying factors based on insights from animal studies. A systematic review of genetic studies on alcoholic pancreatitis was conducted and the results were analyzed in the context of animal studies.


RESULTS
To date, no major genetic cofactors for susceptibility or progression have been identified in approximately 90% of cases of human alcoholic chronic pancreatitis. Mutations have been identified in the pancreatic secretory trypsin inhibitor gene (SPINK1) in about 8% of cases, and an excess in cystic fibrosis transmembrane conductance inhibitor (CFTR) gene variants have been reported, but the details of the complex genetics with CFTR have not been clarified. None of the polymorphisms in alcohol-metabolizing genes or detoxifying genes appear to explain pancreatic susceptibility.


CONCLUSIONS
New, adequately powered genetic studies are needed. Several major genetic epidemiology studies are underway in both Europe and the United States to help determine why only a subset of alcoholics develop alcoholic chronic pancreatitis.
Whitcomb
David C
DC
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. whitcomb@pitt.edu
D000208:Acute Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008954:Models, Biological; D019512:Pancreatitis, Alcoholic / Q000235:genetics* / Q000503:physiopathology; D050500:Pancreatitis, Chronic / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics*
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic