Chronic pancreatitis is a progressive inflammatory disease in which pancreatic secretory parenchyma is destroyed and replaced by fibrous tissue, eventually leading to
malnutrition and diabetes. Alcohol is the leading cause in Western countries, but genetic factors are also implicated. Since the identification of mutations in the cationic
trypsinogen (PRSS1) gene as a cause of
hereditary pancreatitis in 1996, we have seen great progress in our understanding of the genetics of
pancreatitis. It has been established that mutations in the genes related to the activation and inactivation of
trypsin(
ogen) such as PRSS1,
serine protease inhibitor Kazal type 1 (
SPINK1) and
chymotrypsin C (CTRC) genes are associated with
pancreatitis. In 2013,
carboxypeptidase A1 (CPA1) was identified as a novel
pancreatitis susceptibility gene. Endoplasmic reticulum stress in pancreatic acinar cells resulting from the mis-folding of mutated pancreatic
enzymes has been shown to act as a novel mechanism underlying the susceptibility to
pancreatitis. In Japan, the nationwide survey revealed 171 patients (96 males and 75 females) with
hereditary pancreatitis in 59 families based on the European Registry of
Hereditary Pancreatitis and Familial
Pancreatic Cancer criteria. Because about 30% of families with
hereditary pancreatitis do not carry mutations in any of the known
pancreatitis susceptibility genes, other yet unidentified genes might be involved. Next generation sequencers can perform billions of sequencing reactions with a read length of 150-250
nucleotides. Comprehensive analysis using next generation sequencers will be a promising strategy to identify novel
pancreatitis-associated genes and further clarify the pathogenesis of
pancreatitis.