Genetic Risk Factors in Early-Onset Nonalcoholic Chronic Pancreatitis: An Update

Abstract

Chronic pancreatitis (CP) is a progressive, irreversible inflammatory disorder of the pancreas, which results from interrelations between different genetic and environmental factors. Genetic variants are the primary cause of the disease in early-onset nonalcoholic CP patients. Novel CP-associated genes are continuously emerging from genetic studies on CP cohorts, providing important clues for distinct mechanisms involved in CP development. On the basis of functional studies, the genetic alterations have been sub-grouped into CP-driving pathological pathways. This review focuses on the concept of CP as a complex disease driven by multiple genetic factors. We will discuss only well-defined genetic risk factors and distinct functional pathways involved in CP development, especially in the context of the early-onset nonalcoholic CP group. The diagnostic implications of the genetic testing will be addressed as well.

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia

“…Less commonly pancreatitis can result from trauma, infections, drugs, toxins, or it can be idiopathic [ 2 ▪ ]. In addition, genetic factors can influence the risk of pancreatitis [ 4 ▪▪ , 5 ▪ , 6 ▪ , 7 ▪▪ , 8 ▪ , 9 ▪ ], including pathogenic rare variants that cause hereditary forms of pancreatitis, and both rare and common genetic noncausal variants that predispose to pancreatitis either directly or as drivers of its risk factors (see Table 1 ). Other factors that may influence expression of pancreatitis include gene–gene interactions, epigenetic or environmental influences, and individual patient attributes [ 2 ▪ , 7 ▪▪ ].…”

“…Patients with both a severe and mild CFTR pathogenic variant are more likely to present with episodes of acute pancreatitis [ 25 ]. Heterozygous carriers of either CFTR p.Phe508del or p.Arg117His have also been found to be enriched among chronic pancreatitis patients, with reported odds ratios of ∼2–3 [ 8 ▪ ]. Because they are relatively common across geographic ancestries, screening for heterozygous CFTR variants in hypertriglyceridemia-associated pancreatitis may be worthwhile.…”

Variants APOA5 p.G185C and p.S19W associated with early-onset severe hypertriglyceridemia-induced pancreatitis and diabetes complications in a Vietnamese girl

“…(glycosylphosphatidylinositolanchored high-density lipoprotein binding protein 1) were reported to be associated with HTG and a predisposition to pancreatitis risk (Dron, Hegele, 2020). The CFTR gene encoding for cystic fibrosis transmembrane regulator has also been reported to be a gene that is associated with pancreatic and respiratory diseases (Wang et al, 2014;Wertheim-Tysarowska et al, 2021).…”