Genetic polymorphisms in alcoholic pancreatitis.
Chronic, excessive alcohol consumption is clearly associated with acute and chronic pancreatitis. However, both clinical and laboratory studies have demonstrated that alcohol consumption alone does not directly cause pancreatitis. Growing evidence suggests that environmental and possibly genetic cofactors must also be present before the mechanisms protecting the pancreas from pancreatitis are circumvented and pancreatitis develops. The discovery that mutations in the cationic trypsinogen gene (R122H, N29I) predisposed to acute and chronic pancreatitis focused attention on possible genetic predispositions. Mutations in the cationic trypsinogen gene, however, are rarely associated with alcoholic chronic pancreatitis. Mutations in the SPINK1 gene (e.g. N34S) provide a threefold increased risk, and cystic fibrosis transmembrane conductance regulator (CFTR) mutations continue to be investigated. However, the major cofactor associated with alcoholic chronic pancreatitis is yet to be identified.
Hanck
Christoph
C
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, PUH, University of Pittsburgh, 571 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Schneider
Alexander
A
Whitcomb
David C
DC
D000208:Acute Disease; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002352:Carrier Proteins; D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006680:HLA Antigens; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D019512:Pancreatitis, Alcoholic / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000235:genetics
C505032:CFTR protein, human; D002352:Carrier Proteins; D006680:HLA Antigens; D036341:Intercellular Signaling Peptides and Proteins; C486642:SPINK1 protein, human; D000515:alpha 1-Antitrypsin; C064831:PRSS2 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; D000426:Alcohol Dehydrogenase; D014357:Trypsin