Genetic Polymorphisms in Alcoholic PancreatitisWhitcomb D.C.
Departments of Medicine, Cell Biology and Physiology and Human Genetics, University of Pittsburgh, Pittsburgh, Pa., USA
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 ∼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.
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