Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations

Abstract

Objectives To assess whether the age of onset was associated with unique features or disease course in pediatric acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Study design Demographic and clinical information on children with ARP or CP was collected at INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers. The Cochran-Armitage trend test and Jonckheere-Terpstra test were used to examine for differences between pediatric age groups (<6, 6–11 and ≥12 years). Results Between September 2012 and March 2016, 342 children with ARP or CP were enrolled; 129 (38%) were <6 y/o at the time of first diagnosis of acute pancreatitis (AP), 111 (32%) were 6–11 y/o and 102 (30%) were ≥12 y/o. Early onset disease was associated with mutations in cationic trypsinogen (PRSS1) (p<0.01), chymotrypsin C (CTRC) (p=0.01), family history of AP (p=0.02), family history of CP (p<0.01), biliary cysts (p=0.04) or chronic renal failure (p=0.02). Later onset disease was more commonly present with hypertriglyceridemia (p=0.04), ulcerative colitis (p=0.02), autoimmune diseases (p<0.0001) or medication use (p<0.01). Children with later onset disease were also more likely to visit emergency room (p<0.05) or have diabetes (p<0.01). Conclusions Early onset pancreatitis is strongly associated with PRSS1 or CTRC mutations and family history of pancreatitis. Children with later onset disease are more likely to have non-genetic risk factors. Future studies are needed to investigate whether the disease course, response to therapy or clinical outcomes differ relative to the timing of disease onset.

Evaluation of the Pathogenic Significance of the Novel p.T58M Chymotrypsin C Variant in Recurrent Acute Pancreatitis

“…However, genetic susceptibility plays a predominant role in the etiology of childhood onset pancreatitis [5,6], recent publications showed the significance of genetic background in some unusual cases of late onset pancreatitis [7,8]. Biochemical characterisation of novel mutations of known susceptibility genes associated with pancreatitis might help us to evaluate the clinical significance of unknown variants.…”

Development of understanding of DOHaD concepts in students during undergraduate health professional programs in Japan and New Zealand

“…Trends toward 'Yes' response and the higher value on the ordinal variable across undergraduate courses within each country were assessed using the Cochran-Armitage test of trend for binomial responses, and the Jonckheere-Terpstra test of trend for ordinal responses. [16][17][18] The significance threshold was 0.05. Statistical analyses were performed using Excel 2011 (Microsoft) with Statcel 4 add-on (The Publisher OMS Limited, Saitama, Japan) and EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) and SPSS (IBM Corp, 2015).…”

Chronic pancreatitis

“…In one large study of the causes of chronic pancreatitis, alcohol accounted for around 60% of all cases of chronic pancreatitis in men, but only 28% in women, who were much more likely to have an idiopathic diagnosis 34. The aetiology of chronic pancreatitis varies by sex, based on both differences in environmental exposure (alcohol and smoking) 5 and genetic factors 6…”