title: Genetics of pancreatitis with a focus on the pancreatic ducts.
abstract: Genetic risk for acute pancreatitis (AP), recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are increasingly recognized. The exocrine pancreas is composed of both acinar cells and duct cells, with genetic factors associated with AP, RAP and CP linked to one cell type or the other. Increased susceptibility to pancreatitis occurs when the normal physiological mechanisms that allow the pancreas to respond to common stresses or injury are altered. Currently, most our knowledge about genetics focuses on three genes that play critical roles in pancreatic function (PRSS1, CFTR, SPINK1) such that isolated defects lead to disease. However, recent data suggest that more complex combination of genetic and environmental factors are also as important, or more important than Mendelian genetic risk. Understanding of complex interactions requires modeling of these factors so that the response to stresses or injury can be simulated and critical interactions understood. A simple duct cell model is given to illustration the relationship between CFTR, CASR, aquaporins, claudins, and SPINK1, and how they interact. The role of CFTR variants in pancreatic diseases is then discussed.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Larusch
authors.forename: D C
authors.initials: DC
authors.lastname: Whitcomb
mesh_terms: D000208:Acute Disease; D000483:Alleles; D020346:Aquaporins / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D057167:Claudins / Q000235:genetics; D003550:Cystic Fibrosis / Q000150:complications; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010183:Pancreatic Ducts / Q000503:physiopathology; D010195:Pancreatitis / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D050500:Pancreatitis, Chronic / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D014357:Trypsin / Q000235:genetics*; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D020346:Aquaporins; D015415:Biomarkers; C505032:CFTR protein, human; D002352:Carrier Proteins; D057167:Claudins; D044169:Receptors, Calcium-Sensing; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; C489303:PRSS1 protein, human; D014357:Trypsin