Acute Pancreatitis: Genetic Risk and Clinical Implications

Abstract

Acute pancreatitis (AP) is one of the most common gastroenterological indications for emergency admittance and hospitalization. Gallstones, alcohol consumption or the presence of additional initiating factors give rise to a disease with a diverse clinical appearance and a hard-to predict course of progression. One major challenge in the treatment of AP patients is the early identification of patients at risk for the development of systemic complications and organ failure. In addition, 20%–30% of patients with a first episode of AP later experience progress to recurrent or chronic disease. Complex gene–environment interactions have been identified to play a role in the pathogenesis of pancreatitis, but so far no predictive genetic biomarkers could be implemented into the routine clinical care of AP patients. The current review explains common and rare etiologies of acute pancreatitis with emphasis on underlying genetic aberrations and ensuing clinical management.

Association Between Ascites and Clinical Findings in Patients with Acute Pancreatitis: A Retrospective Study

“…Thus, we fell short of assessing the association between ascites characteristics (such as its volume) and AP complications. Second, although we analyzed the clinical data to our best abilities, we did not consider genetic factors, such as mutations of SPINK1, IL-1b, IL-10, which greatly influence the risk, etiology, and severity of AP [ 32 ]. Third, this was a single-center study with a small cohort.…”

CNest: A Novel Copy Number Association Discovery Method Uncovers 862 New Associations from 200,629 Whole Exome Sequence Datasets in the UK Biobank

“…Another example is ICD10 code D50: iron deficiency anaemia we discovered two significantly associated loci on chromosome 7 (Figure 3F) one of which covers exons 4-6 of the cationic trypsinogene gene PRSS1 that has been linked to chronic pancreatitis by multiple studies (125,126). Autosomal dominant mutations in PRSS1 are thought to be a leading cause of hereditary pancreatitis, a rare condition that results in recurrent inflammation of the pancreas, and an increased risk of pancreatic cancer (127).…”

Pancreatic Associated Manifestations in Pediatric Inflammatory Bowel Diseases

“…An impairment in SPINK1 expression has been also associated with sustained trypsin activity over time, thus leading to an increased risk of recurrence and progression of the disease [ 30 ]. Variants in SPINK1 N34S haplotype, present with a prevalence of 1–2% in the healthy population [ 33 ], have been particularly associated with a faster progression to ARP, along with an increased risk of CP by approximately 10-fold [ 30 ]. Similar evidence has been observed for CFTR, PRSS1, CTRC, and carboxypeptidase 1 gene mutations, which seem to predispose children to early-onset CP [ 29 , 34 ].…”

“…A recent systematic search of the literature and meta-analysis identified a significant association of SPINK1, Aldehyde Dehydrogenase 2 (ALDH2), interleukin (IL)-1B, IL-6, and IL-18 variants with the risk for AP, while variants in TNF, GSTP1 and CXCL8 were associated with disease severity [ 35 ]. Polymorphisms in the promoter regions of IL-1B, IL-6, IL-8, and IL-10 have been furthermore related to a more severe course of the disease [ 33 ].…”

“…Anyhow, in the clinical practice genetic testing is generally considered for individuals with manifested symptoms of CP or recurrent acute pancreatitis. Patients presenting with a first episode of acute pancreatitis should also be considered when they are young (<18 years), with a family history of pancreatitis or when family members are asymptomatic carriers of mutations that are known to be associated with hereditary pancreatitis (HP) [ 33 ].…”