Logo image
Back
Pancreatitis Risk Genes Play a Major Role in Pediatric Pancreatitis: Insights From INSPPIRE
Journal article   Open access   Peer reviewed

Pancreatitis Risk Genes Play a Major Role in Pediatric Pancreatitis: Insights From INSPPIRE

Maisam Abu-El-Haija, Wenying Zhang, Fuchenchu Wang, Gretchen Cress, Brian Dawson, Xiaoping Su, Tyler Thompson, Nicole Kotha, Ankur Chugh, Reuven Zev Cohen, …
Clinical gastroenterology and hepatology
06/16/2026
DOI: 10.1016/j.cgh.2026.06.004
PMID: 42303027
url
https://doi.org/10.1016/j.cgh.2026.06.004View
Published (Version of record) Open Access

Abstract

Clinical data show that genetic variants are significant risk factors for acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). To expand understanding of the role of genetics in ARP and CP, high-throughput next-generation sequencing of 14 genes was completed in a multi-center pediatric cohort. A cross-sectional study involving 944 pediatric ARP or CP subjects was conducted. CASR, CEL, CFTR, CLDN2, CPA1, CTRC, GGT1, PRSS1, PRSS2, PRSS3, SBDS, SLC26A9, SPINK1, and UBR1 were sequenced. The frequencies of identified variants were compared with frequencies in the gnomAD database. Group differences were calculated by odd ratios (OR), relative risks (RR), and one-tailed Fisher's exact test with false discovery rate (FDR) adjusted p-values. A total of 120 variants, including 79 never previously reported to be associated with pancreatitis, had an increased odd, with OR>1, (FDR≤0.01) compared with gnomAD. Of these, 38 focused variants found in CFTR (10 variants), PRSS1 (6), CTRC (6), SPINK1 (5), PRSS3 (3), GGT1 (3), CASR (2), CPA1 (2), and PRSS2 (1) were included for further analysis. Seventy-four percent of children with ARP or CP carried at least one genetic risk variant. In the ARP group, CASR (p=0.005) and CPA1 (p<0.001) contained the most prevalent variants. In CP, CTRC (p=0.012) and PRSS1 (p<0.001) variants were most common. The presence of any genetic risk variant was associated with faster disease progression from AP to CP compared to none (p=0.014). Variants in PRSS1, CTRC and SPINK1 significantly increased progression to CP. Our findings highlight the importance of assessing genetic risk variants in children with pancreatitis.
 Genetics acute recurrent pancreatitis chronic pancreatitis Pediatric pancreatitis risk variants

Details

Metrics

3 Record Views
Logo image