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

Abstract

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.