Genetics of pancreatitis

Abstract

Purpose of review Chronic pancreatitis is a syndrome characterized by chronic inflammation of the pancreas, with variable pain, calcifications, necrosis, fatty replacement, fibrosis and scarring and other complications. Disease susceptibility, severity, progression and pain patterns vary widely and do not necessarily parallel one another. Much of the variability in susceptibility to recurrent acute and chronic pancreatitis is now clearly shown to be related to genetic differences between patients. This review highlights recent advances and future directions in genetic research. Recent findings The strongest risk factors are associated with genetic variations in PRSS1, SPINK1, CFTR, and to a lesser extent, CTRC and CASR. The latest research suggest that a single factor rarely causes pancreatitis, and the majority of patients with recurrent acute and chronic pancreatitis have multiple variants in a gene, or epistatic interactions between multiple genes, coupled with environmental stressors. Summary Pancreatic diseases have a strong genetic component. Rather than a classic Mendelian disorder, recurrent acute and chronic pancreatitis represents truly complex diseases with the interaction and synergism of multiple genetic and environmental factors. The future will require new predictive models to guide prevention and therapy.

Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1

“…While excessive alcohol consumption and gallstone obstruction of the pancreatic duct are known causes of pancreatitis, a significant genetic component influences both idiopathic and environmentally-related cases of pancreatitis (28,51). Several rodent models have been established to identify early initiating events for pancreatitis, including supramaximal secretagogue stimulation, ductal ligation, and L-arginine injection (5,26,38,44).…”

Association of the HindIII Lipoprotein Lipase Gene Polymorphism with the Development of the Non-Biliary Acute Pancreatitis: a Pilot Study

“…ANP is a multifactorial disease; its development is determined by a complex interaction of multiple genes and various environmental factors [10]. Genetic mechanisms of ANP and its complications are poorly understood [1,10].…”

Letter to the editor

“…3 The reason for this has recently been demonstrated in studies showing that, at least in humans and rodents, SPINK1 is only expressed at very low levels in normal acinar cells. 4 Its expression is up-regulated as a protective measure in the context of active pancreatic inflammation. This is an interesting observation which has not been investigated in dogs to date.…”

“…However, if SPINK1 mutations occur concurrently with other milder mutations such as mild CFTR mutations, the risk of pancreatitis is increased. To quote LaRush and Whitcomb 2011, 4 'It is critical to note that although the individual risk of pancreatitis among either SPINK1 or CTFR single mutation carriers is 2-4 fold, carrier frequency is 2-5% each and 99% of carriers are healthy. However, with concurrent multiple SPINK1/ CFTR variants the risk is synergistic, mutation specific and healthy carriers of multiple mutations are exceptionally rare'.…”