Genetics of acute and chronic pancreatitis

Abstract

Purpose of review Acute pancreatitis (AP), recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are interrelated and progressive inflammatory disorders of the pancreas with highly variable and complex susceptibility, severity and outcomes. The role of genetics in AP, RAP and progression to CP within a new framework is needed. Recent findings The first genome-wide association study in pancreas has been published with genome-wide significance linked with non-coding variants at the PRSS1-PRSS2 locus on chromosome 7 and the CLDN2 locus on the X chromosome. A new personalized medicine paradigm is considered to facilitate organization of genetic and other susceptibility risk compared to risk of disease progression or resolution and risk of complications. Summary A new framework for organizing multiple, complex data sets is emerging. The role of genetics in the context of other variables, is important in understanding susceptibility to RAP and in the modification of disease severity and progression to CP. Questions of when to order testing, what to order and how to use the data in real time remains an area for future research and development.

Genetic determination of pancreatitis

“…The results of studies provide sufficient evidence that AP may progress to a chronic process with changeable speed, according to the frequency of recurrent acute episodes, severity of the course of the disease, and the type of immune response [13,27]. The risk factors playing a special role in the progression of AP to CP are alcohol consumption and tobacco smoking, as well as various genetic variants [12,28].…”

“…According to Mouzner [13], it seems justifiable to consider a delay in the performance of cholecystectomy in the group of patients with indications for genetic testing using the NGS technology until obtaining the results of genotyping. Also, the guidelines by the Polish Pancreatic Club recommend the performance of genetic tests (PRSS1, CFTR, SPINK1) in young patients with a family history of recurrent AP [19].…”

“…The potential genetic risk is specified based on the family history of AP, RAP, CP, cystic fibrosis, hypertriglyceridaemia, and pancreatic cancer [13]. The use of genetic information, including modern methods of DNA sequencing, such as next-generation sequencing (NGS), is still difficult to apply in order to explain the first episode of AP, but it has become a valuable source of information for the assessment of RAP and CP [13]. Various groups of genetic mutations may play a role in the pathogenesis of pancreatitis.…”

Patients With Sentinel Acute Pancreatitis of Alcoholic Etiology Are at Risk for Organ Failure and Pancreatic Necrosis

“…9,27,28 Emerging evidence indicates that genetic polymorphisms play a role in susceptibility to alcoholic AP. [28][29][30] Of note, this research focuses on mechanisms of direct acinar toxicity.…”

Risk Factors for Pancreatic Cancer: Underlying Mechanisms and Potential Targets

“…Cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel, allows the movement of chloride and bicarbonate from ductal cells to the ductal lumen. In mutations of CFTR that lead to decreased bicarbonate conductance, but not chloride, there is a higher risk of idiopathic CP especially when paired with mutation of SPINK1 (Mounzer and Whitcomb, 2013). Ethanol has been shown to reduce CFTR function via depletion of ATP (Judak et al, 2013).…”