The Differential Role of Human Cationic Trypsinogen (PRSS1) p.R122H Mutation in Hereditary and Nonhereditary Chronic Pancreatitis: A Systematic Review and Meta-Analysis

Abstract

Background Environmental factors and genetic mutations have been increasingly recognized as risk factors for chronic pancreatitis (CP). The PRSS1 p.R122H mutation was the first discovered to affect hereditary CP, with 80% penetrance. We performed here a systematic review and meta-analysis to evaluate the associations of PRSS1 p.R122H mutation with CP of diverse etiology. Methods The PubMed, EMBASE, and MEDLINE database were reviewed. The pooled odds ratio (OR) with 95% confidence intervals was used to evaluate the association of p.R122H mutation with CP. Initial analysis was conducted with all etiologies of CP, followed by a subgroup analysis for hereditary and nonhereditary CP, including alcoholic or idiopathic CP. Results A total of eight case-control studies (1733 cases and 2415 controls) were identified and included. Overall, PRSS1 p.R122H mutation was significantly associated with an increased risk of CP (OR = 4.78[1.13–20.20]). Further analysis showed p.R122H mutation strongly associated with the increased risk of hereditary CP (OR = 65.52[9.09–472.48]) but not with nonhereditary CP, both alcoholic and idiopathic CP. Conclusions Our study showing the differential role of p.R122H mutation in various etiologies of CP indicates that this complex disorder is likely influenced by multiple genetic factors as well as environmental factors.

A high prevalence of genetic polymorphisms in idiopathic and alcohol-associated chronic pancreatitis patients in Ireland

“…Variable rates of PRSS1 gene mutations have been reported in chronic pancreatitis patients of idiopathic etiology (0-21%). 14,[25][26][27][28] Similar to the current findings, several studies internationally have reported that PRSS1 mutations were rare or absent in patients with chronic pancreatitis, [28][29][30][31][32][33] although others reported PRSS1 mutations at frequencies of 1.5-33% amongst alcohol-related pancreatitis patients. 27,34 SPINK1 mutations are found in 1-3% of the general population, 24 and idiopathic chronic pancreatitis is strongly associated with the common SPINK1 high-risk genotype N34S.…”

WITHDRAWN: Clinical interpretation of PRSS1 gene variants in patients with pancreatitis

“…It was also suggested that autoimmune pancreatitis may be related to PRSS1 variants [12]. However, a recent large metaanalysis has shown that one of the most frequent PRSS1 variant, p.R112H, was strongly associated with an increased risk of hereditary CP but not with sporadic CP, either alcoholic or idiopathic [13].…”

Biochemical and Molecular Characterization of Eel Fish Trypsin (Anguilla bicolor McClelland) as Potential Candidates Protease Enzyme

“…According to [33] and [34], the gene encoding the serine protease enzyme group is the PRSS1 gene. This gene encodes trypsinogen, a member of the serine protease trypsin family.…”