Genetics of acute and chronic pancreatitis: An update

Abstract

Progress made in identifying the genetic susceptibility underlying acute and chronic pancreatitis has benefitted the clinicians in understanding the pathogenesis of the disease in a better way. The identification of mutations in cationic trypsinogen gene (PRSS1 gene; functional gain mutations) and serine protease inhibitor kazal type 1 (SPINK1 gene; functional loss mutations) and other potential susceptibility factors in genes that play an important role in the pancreatic secretory functions or response to inflammation during pancreatic injury has changed the current concepts and understanding of a complex multifactorial disease like pancreatitis. An individual’s susceptibility to the disease is governed by genetic factors in combination with environmental factors. Candidate gene and genetic linkage studies have identified polymorphisms in cationic trypsinogen (PRSS1), SPINK1, cystic fibrosis trans-membrane conductance regulator (CFTR), Chymotrypsinogen C (CTRC), Cathepsin B (CTSB) and calcium sensing receptor (CASR). Individuals with polymorphisms in the mentioned genes and other as yet identified genes are at an enhanced risk for the disease. Recently, polymorphisms in genes other than those involved in “intra-pancreatic trypsin regulatory mechanism” namely Claudin-2 (CLDN2) and Carboxypeptidase A1 (CPA1) gene have also been identified for their association with pancreatitis. With ever growing number of studies trying to identify the genetic susceptibility in the form of single nucleotide polymorphisms, this review is an attempt to compile the available information on the topic.

Keywords: Chronic pancreatitis, Acute pancreatitis, Genetic susceptibility, Single nucleotide polymorphisms, Inflammation

Core tip: Pancreatitis is a progressive inflammatory disease. Though the pancreas has adequate protection against environmental and metabolic stress, if the magnitude of this stress exceeds the threshold which the organ can handle, it leads to pathologic effects. Although genetic variables have been identified that affect the function of pancreas, namely polymorphisms in serine protease inhibitor kazal type 1 (SPINK1), polymorphisms in cationic trypsinogen (PRSS1) and Chymotrypsinogen C (CTRC) genes in the acinar cells and cystic fibrosis trans-membrane conductance regulator (CFTR), calcium sensing receptor (CASR genes) in the ductal cells leading to pancreatitis, off late many genetic factors outside of the “intra-pancreatic trypsin regulatory mechanism” have been identified for their role in pancreatitis. This review is an update on the genetic aspects of acute and chronic pancreatitis.