Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis

Frank Ulrich Weiss, Nico Hesselbarth, Andrea Párniczky, Dora Mosztbacher, Felix Lämmerhirt, Claudia Ruffert, Peter Kovacs, Sebastian Beer, Katharina Seltsam, Heidi Griesmann, Richard Böhme, Tom Kaune, Marcus Hollenbach, Hans Ulrich Schulz, Peter Simon, Julia Mayerle, Markus M. Lerch, Giulia Martina Cavestro, Raffaella Alessia Zuppardo, Milena Di LeoPier Alberto Testoni, Ewa Malecka-Panas, Anita Gasirowska, Stanislaw Głuszek, Peter Bugert, Andrea Szentesi, Joachim Mössner, Heiko Witt, Patrick Michl, Peter Hégyi, Markus Scholz, Jonas Rosendahl

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background/Objectives: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. Methods: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. Results: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81–0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07–1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12–1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63–0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07–1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07–1.93, p-value 0.02) in the alcoholic sub-group only. Conclusions: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.

Original languageEnglish
Pages (from-to)477-481
Number of pages5
JournalPancreatology
Volume18
Issue number5
DOIs
StatePublished - Jul 2018

Keywords

  • Acute pancreatitis
  • Genetics
  • Risk factors
  • Single nucleotide polymorphisms

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