Genetic susceptibility to post-endoscopic retrograde cholangiopancreatography pancreatitis identified in propensity score-matched analysis
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Background/Aims: A previous history of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a risk factor for PEP, suggesting that there may be a genetic predisposition to PEP. However, nothing is known about this yet. The aim of this study was to identify genetic variations associated with PEP. Methods: A cohort of high-risk PEP patients was queried from December 2016 to January 2019. For each PEP case, two propensity score-matched controls were selected. Whole exome sequencing was performed using blood samples. Genetic variants reported to be related to pancreatitis were identified. To discover genetic variants that predispose to PEP, a logistic regression analysis with clinical adjustment was performed. Gene-wise analyses were also conducted. Results: Totals of 25 PEP patients and 50 matched controls were enrolled. Among the genetic variants reported to be associated with pancreatitis, only CASR rs1042636 was identified, and it showed no significant difference between the case and control groups. A total of 54,269 non-synonymous variants from 14,313 genes was identified. Logistic regression analysis of these variants showed that the IRF2BP1 rs60158447 GC genotype was significantly associated with the occurrence of PEP (odds ratio 2.248, FDR q value = 0.005). Gene-wise analyses did not show any significant results. Conclusions: This study found that the IRF2BP1 gene variant was significantly associated with PEP. This genetic variant is a highly targeted PEP risk factor candidate and can be used for screening high-risk PEP groups before ERCP through future validation. (ClinicalTrials.gov no. NCT02928718)
Abstract
Background/Aims: A previous history of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a risk factor for PEP, suggesting that there may be a genetic predisposition to PEP. However, nothing is known about this yet. The aim of this study was to identify genetic variations associated with PEP. Methods: A cohort of high-risk PEP patients was queried from December 2016 to January 2019. For each PEP case, two propensity score-matched controls were selected. Whole exome sequencing was performed using blood samples. Genetic variants reported to be related to pancreatitis were identified. To discover genetic variants that predispose to PEP, a logistic regression analysis with clinical adjustment was performed. Gene-wise analyses were also conducted. Results: Totals of 25 PEP patients and 50 matched controls were enrolled. Among the genetic variants reported to be associated with pancreatitis, only CASR rs1042636 was identified, and it showed no significant difference between the case and control groups. A total of 54,269 non-synonymous variants from 14,313 genes was identified. Logistic regression analysis of these variants showed that the IRF2BP1 rs60158447 GC genotype was significantly associated with the occurrence of PEP (odds ratio 2.248, FDR q value = 0.005). Gene-wise analyses did not show any significant results. Conclusions: This study found that the IRF2BP1 gene variant was significantly associated with PEP. This genetic variant is a highly targeted PEP risk factor candidate and can be used for screening high-risk PEP groups before ERCP through future validation. (ClinicalTrials.gov no. NCT02928718)
참고문헌 (36)
- Freeman ML, "Prevention of post-ERCP pancreatitis : a comprehensive review", Gastrointest Endosc, 59, pp.845~864 (2004)
- Kochar B, "Incidence, severity, and mortality of post-ERCP pancreatitis : a systematic review by using randomized, controlled trials", Gastrointest Endosc, 81, pp.143~149 (2015)
- Ribeiro IB, "Pancreatitis after endoscopic retrograde cholangiopancreatography : a narrative review", World J Gastroenterol, 27, pp.2495~2506 (2021)
- Tae Young Park, "Rectal NSAIDs-based combination modalities are superior to single modalities for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a network meta-analysis", The Korean Journal of Internal Medicine, 37(2), pp.322~339 (2022), 대한내과학회[DOI]
- Chen JJ, "Risk factors for post-ERCP pancreatitis : a systematic review of clinical trials with a large sample size in the past 10 years", Eur J Med Res, 19, pp.26~ (2014)
- Mystakidis K, "Is post-ERCP pancreatitis a genetically predisposed complication?", Gastroenterol Res Pract, 2012, pp.473960~ (2012)
- Angsuwatcharakon P, "The polymorphisms at PRSS1-PRSS2 and MORC4 loci and the risk of post-ERCP pancreatitis", Gastroenterol Res Pract, 2018, pp.1064783~ (2018)
- Goodwin S, "Coming of age : ten years of next-generation sequencing technologies", Nat Rev Genet, 17, pp.333~351 (2016)
- Elmunzer BJ, "A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis", N Engl J Med, 366, pp.1414~1422 (2012)
- Cotton PB, "Endoscopic sphincterotomy complications and their management : an attempt at consensus", Gastrointest Endosc, 37, pp.383~393 (1991)
- Gorry MC, "Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis", Gastroenterology, 113, pp.1063~1068 (1997)
- Grocock CJ, "The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families", Gut, 59, pp.357~363 (2010)
- Kume K, "A loss-of-function p. G191R variant in the anionic trypsinogen(PRSS2)gene in Japanese patients with pancreatic disorders", Gut, 58, pp.820~824 (2009)
- O’Reilly DA, "The SPINK1 N34S variant is associated with acute pancreatitis", Eur J Gastroenterol Hepatol, 20, pp.726~731 (2008)
- Sharer N, "Mutations of the cystic fibrosis gene in patients with chronic pancreatitis", N Engl J Med, 339, pp.645~652 (1998)
- Schneider A, "Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis", Gastroenterology, 140, pp.162~171 (2011)
- Rosendahl J, "Chymotrypsin C(CTRC)variants that diminish activity or secretion are associated with chronic pancreatitis", Nat Genet, 40, pp.78~82 (2008)
- LaRusch J, "Genetics of pancreatitis", Curr Opin Gastroenterol, 27, pp.467~474 (2011)
- Stepanchick A, "Calcium sensing receptor mutations implicated in pancreatitis and idiopathic epilepsy syndrome disrupt an arginine-rich retention motif", Cell Physiol Biochem, 26, pp.363~374 (2010)
- Witt H, "Variants in CPA1 are strongly associated with early onset chronic pancreatitis", Nat Genet, 45, pp.1216~1220 (2013)
- "FastQC: a quality control tool for high throughput sequence data" (2010)[URL]
- Li H, "Fast and accurate short read alignment with Burrows-Wheeler transform", Bioinformatics, 25, pp.1754~1760 (2009)
- "Picard toolkit" (2019)[URL]
- McKenna A, "The Genome Analysis Toolkit : a MapReduce framework for analyzing next-generation DNA sequencing data", Genome Res, 20, pp.1297~1303 (2010)
- Cingolani P, "A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3", Fly(Austin), 6, pp.80~92 (2012)
- Thorvaldsdóttir H, "Integrative Genomics Viewer(IGV) : high-performance genomics data visualization and exploration", Brief Bioinform, 14, pp.178~192 (2013)
- Seo H, "Deleterious genetic variants in ciliopathy genes increase risk of ritodrine-induced cardiac and pulmonary side effects", BMC Med Genomics, 11, pp.4~ (2018)
- Lee S, "Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies", Am J Hum Genet, 91, pp.224~237 (2012)
- 1000 Genomes Project Consortium, "A global reference for human genetic variation", Nature, 526, pp.68~74 (2015)
- Childs KS, "Identification of novel co-repressor molecules for Interferon Regulatory Factor-2", Nucleic Acids Res, 31, pp.3016~3026 (2003)
- Yeung KT, "A novel transcription complex that selectively modulates apoptosis of breast cancer cells through regulation of FASTKD2", Mol Cell Biol, 31, pp.2287~2298 (2011)
- Barysch SV, "Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling", EMBO Rep, 22, pp.e49651~ (2021)
- Mashima H, "Interferon regulatory factor-2 regulates exocytosis mechanisms mediated by SNAREs in pancreatic acinar cells", Gastroenterology, 141, pp.1102~1113 (2011)
- Gaisano HY, "New insights into the mechanisms of pancreatitis", Gastroenterology, 136, pp.2040~2044 (2009)
- Muddana V, "Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population : role of serine protease inhibitor Kazal 1type and alcohol", World J Gastroenterol, 14, pp.4486~4491 (2008)
- Scillitani A, "Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor", J Clin Endocrinol Metab, 89, pp.5634~5638 (2004)
