• Fons F van den Berg, Yama Issa, Jeroen P Vreijling, Markus M Lerch, Frank Ulrich Weiss, Marc G Besselink, Frank Baas, Marja A Boermeester, Hjalmar C van Santvoort, and Dutch Pancreatitis Study Group.
• Department of Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
• Ann. Surg. 2022 Jun 1; 275 (6): e781e788e781-e788.

ObjectiveThe aim of this study was to identify genetic variants associated with early multiple organ failure (MOF) in acute pancreatitis.Summary Background DataMOF is a life-threatening complication of acute pancreatitis, and risk factors are largely unknown, especially in early persistent MOF. Genetic risk factors are thought to enhance severity in complex diseases such as acute pancreatitis.MethodsA 2-phase study design was conducted. First, we exome sequenced 9 acute pancreatitis patients with early persistent MOF and 9 case-matched patients with mild edematous pancreatitis (phenotypic extremes) from our initial Dutch cohort of 387 patients. Secondly, 48 candidate variants that were overrepresented in MOF patients and 10 additional variants known from literature were genotyped in a replication cohort of 286 Dutch and German patients.ResultsExome sequencing resulted in 161,696 genetic variants, of which the 38,333 non-synonymous variants were selected for downstream analyses. Of these, 153 variants were overrepresented in patients with multiple-organ failure, as compared with patients with mild acute pancreatitis. In total, 58 candidate variants were genotyped in the joined Dutch and German replication cohort. We found the rs12440118 variant of ZNF106 to be overrepresented in patients with MOF (minor allele frequency 20.4% vs 11.6%, Padj=0.026). Additionally, SLC52A1 rs346821 was found to be overrepresented (minor allele frequency 48.0% vs 42.4%, Padj= 0.003) in early MOF. None of the variants known from literature were associated.Conclusions: This study indicates that SLC52A1, a riboflavin plasma membrane transporter, and ZNF106, a zinc finger protein, may be involved in disease progression toward (early) MOF in acute pancreatitis.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

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