Pancreas Divisum Increases the Risk of Recurrent Acute Pancreatitis in Patients with rs12338 Polymorphism in the Cathepsin B Gene.
Association
Pancreas divisum
Recurrent pancreatitis
Risk allele
Single-nucleotide polymorphism
Journal
Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
26
03
2020
accepted:
22
07
2020
pubmed:
6
8
2020
medline:
9
9
2021
entrez:
6
8
2020
Statut:
ppublish
Résumé
Pancreas divisum (PD) as a cause of pancreatitis has been debated. In this study, we report the association of multiple gene polymorphisms on the risk of RAP in the presence of PD. We enrolled 687 individuals (167 IRAP, 276 ICP, and 244 unrelated healthy controls) from May 2015 to September 2016. Patients were divided into those with/without PD. Associations between the significantly prevalent SNPs and IRAP/ICP in the presence of PD were evaluated. Clinical data were analyzed using Mann-Whitney U/Chi-square test. Effect size of association of SNPs with IRAP/ICP was expressed as odds ratio (OR) (95% CI). Gene-gene interaction was assessed by transheterozygosity analyses. Bonferroni-corrected two-tailed "p" value of ≤ 0.01 was considered statistically significant. Thirty-three (19.8%) and 82 (29.7%) patients with IRAP and ICP, respectively, had PD. Among the patients with IRAP, duration of disease was significantly shorter in those with PD compared to those without (mean [95% CI] duration: 1.6 (1.3-1.9) vs 2.7 (2.3-3.1) years; p = 0.005). There were no differences in gender, race, and diabetes among patients with/without PD in IRAP/ICP groups. Mean (95% CI) pancreatic duct diameter (mm) was significantly higher in the presence of PD in patients with both IRAP [1.6 (1.4-1.9) v/s 1.29 (1.2-1.4); p = 0.03)] and ICP [5.2 (4.5-5.9) v/s 4.5 (3.9-5.1); p = 0.02]. CTSB (rs12338) polymorphisms were significantly associated with IRAP [OR (95% CI) 2.44 (1.41-4.22); p = 0.001] among patients with PD. No association was observed with ICP. Transheterozygosity analysis did not show any significant associations of combination of SNPs with IRAP in the presence of PD. Risk of RAP due to PD increases in patients with rs12338 polymorphism in the cathepsin B gene.
Identifiants
pubmed: 32754840
doi: 10.1007/s10620-020-06517-7
pii: 10.1007/s10620-020-06517-7
doi:
Substances chimiques
Cathepsin B
EC 3.4.22.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2283-2290Références
DiMagno MJ, Wamsteker EJ. Pancreas divisum. Curr Gastroenterol Rep.. 2011;13:150–156.
doi: 10.1007/s11894-010-0170-8
Fogel EL, Toth TG, Lehman GA, et al. Does endoscopic therapy favorably affect the outcome of patients who have recurrent acute pancreatitis and pancreas divisum? Pancreas. 2007;34:21–45.
doi: 10.1097/mpa.0b013e31802ce068
Liao Z, Gao R, Wang W, et al. A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum. Endoscopy. 2009;41:439–444.
doi: 10.1055/s-0029-1214505
Ravi Kanth VV, Reddy DN. Genetics of acute and chronic pancreatitis. World J Gastrointest Pathophysiol. 2014;5:427–437.
doi: 10.4291/wjgp.v5.i4.427
Avanthi US, Bala G, Aslam M, Talukdar R, Duvurr NR, Vishnubhotla RV. PRSS1 (R122H) mutation in an Indian family with low penetrance is associated with pancreatitis phenotype. Indian J Gastroenterol. 2018;37:67–69.
doi: 10.1007/s12664-018-0828-y
Weiss FU, Behn CO, Simon P, et al. Cathepsin B gene polymorphism Val26 is not associated with idiopathic chronic pancreatitis in European patients. Gut. 2007;56:1322–1323.
doi: 10.1136/gut.2007.122507
Garg PK, Khajuria R, Kabra M, et al. Association of SPINK1 gene mutation and CFTR gene polymorphisms in patients with pancreas divisum presenting with idiopathic pancreatitis. J Clin Gastroenterol. 2009;43:848–852.
doi: 10.1097/MCG.0b013e3181a4e772
Bertin C, Pelletier AL, Vullierme MP, et al. Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations. Am J Gastroenterol.. 2012;107:311–317.
doi: 10.1038/ajg.2011.424
Gelrud A, Sheth S, Banerjee S, et al. Analysis of cystic fibrosis gene product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis. Am J Gastroenterol.. 2004;99:1557–1562.
doi: 10.1111/j.1572-0241.2004.30834.x
Cavestro GM, Zuppardo RA, Bertolini S, et al. Connections between genetics and clinical data: role of MCP-1, CFTR, and SPINK-1 in the setting of acute, acute recurrent, and chronic pancreatitis. Am J Gastroenterol. 2010;105:199–206.
doi: 10.1038/ajg.2009.611
Mahurkar S, Idris MM, Reddy DN, et al. Association of cathepsin B gene polymorphisms with tropical calcific pancreatitis. Gut. 2006;55:1270–1275.
doi: 10.1136/gut.2005.087403
Talukdar R, Sareen A, Zhu H, et al. Release of cathepsin B in cytosol causes cell death in acute pancreatitis. Gastroenterology. 2016;151:747–758.
doi: 10.1053/j.gastro.2016.06.042
Jakkampudi A, Jangala R, Reddy R, et al. Acinar injury and early cytokine response in human acute biliary pancreatitis. Sci Rep. 2017;10:15276.
doi: 10.1038/s41598-017-15479-2
Sendler M, Maertin S, John D, et al. Cathepsin B activity initiates apoptosis via digestive protease activation in pancreatic acinar cells and experimental pancreatitis. J Biol Chem. 2016;291:14717–14731.
doi: 10.1074/jbc.M116.718999
Sendler M, Weiss FU, Golchert J, et al. Cathepsin B-mediated activation of trypsinogen in endocytosing macrophages increases severity of pancreatitis in mice. Gastroenterology. 2018;154:704–718.
doi: 10.1053/j.gastro.2017.10.018
Lerch MM, Halangk W. Human pancreatitis and the role of cathepsin B. Gut. 2006;55:1220–1230.