283 Impact of PRSS1 and CLDN2 Variants in Alcoholic Versus Non-Alcoholic Chronic Pancreatitis

Background & Aims: Chronic pancreatitis (CP) is an inflammatory destructive disorder with a complex pathogenesis. In non-alcoholic chronic pancreatitis (NACP) several genetic risk factors have been identified. A genome wide association study reported that PRSS1 (rs10273639; cationic trypsinogen) and CLDN2 (rs7057398 and rs12688220; Claudin 2) variants contribute to CP susceptibility or resistance. Here, we aimed to refine these findings in a large European cohort. Methods: In total, 3,002 alcohol-related (ACP) and NACP patients and 4,523 controls were enrolled. In addition we included 1,560 German patients with alcoholic liver cirrhosis (ALC) or alcohol dependence (AD) for comparison with German ACP patients. We used a logistic regression model to examine genotype-phenotype relationships. Results: The association with ACP was strongest for PRSS1 SNP (OR 0.63, 95% CI [0.58-0.69]). In male ACP patients both CLDN2 SNPs (OR 1.56, [1.45-1.69] and OR 1.51, [1.39-1.63]) associated with the disease. In female ACP patients CLDN2 SNPs were similarly associated (OR 1.51, [1.25-1.84] and OR 1.36, [1.16-1.59)], while the impact was lower. Similar results were obtained for the comparison of German ACP to German ALC and AD patients. In the overall NACP population, the association of the PRSS1 SNP was marginal (OR 0.82, [0.72-0.94]), while only CLDN2 rs12688220 SNP associated with NACP in males (OR 1.52, [1.13-2.06]). Conclusions: Our results implicate that PRSS1 and CLDN2 gene variants are associated with CP and strongly impact ACP, but only marginally affect NACP.