Pancreas Divisum Increases the Risk of Recurrent Acute Pancreatitis in Patients with rs12338 Polymorphism in the Cathepsin B Gene

Dig Dis Sci. 2021 Jul;66(7):2283-2290. doi: 10.1007/s10620-020-06517-7. Epub 2020 Aug 4.

Abstract

Objectives: 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.

Design: 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.

Results: 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.

Conclusion: Risk of RAP due to PD increases in patients with rs12338 polymorphism in the cathepsin B gene.

Keywords: Association; Pancreas divisum; Recurrent pancreatitis; Risk allele; Single-nucleotide polymorphism.

MeSH terms

  • Cathepsin B / genetics
  • Cathepsin B / metabolism*
  • Gene Expression Regulation
  • Genotype
  • Humans
  • Pancreas / abnormalities*
  • Pancreatitis / classification*
  • Pancreatitis / etiology*
  • Pancreatitis / genetics
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • Cathepsin B