Genetic risk factors in chronic pancreatitis

Abstract

Chronic pancreatitis is a persistent inflammatory disorder of the pancreas, characterized by destruction of the pancreatic parenchyma, maldigestion, chronic pain and diabetes mellitus. Genetic factors determining susceptibility to chronic pancreatitis can be classified in two groups: 1. rare gene mutations affecting the cationic trypsinogen gene that directly cause the disease, and 2. genetic variants that increase the risk for chronic pancreatitis but require additional risk factors to precipitate the disease. These gene variants are considered genetic risk factors, which emerged during the past decade and now represent a clinically important etiological category. Susceptibility to chronic pancreatitis is inherited in a complex manner, which can involve alterations in several genes conferring various degrees of risk. The biochemical mechanism behind the genetic risk includes increased ectopic activation of the digestive enzyme trypsin in the pancreas and failure of protective mechanisms responsible for trypsin inactivation.