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

FU Weiss, N Hesselbarth, A Párniczky, D Mosztbacher, F Lämmerhirt, C Ruffert, P Kovacs, S Beer, K Seltsam, H Griesmann, R Böhme, T Kaune, M Hollenbach, HU Schulz, P Simon, J Mayerle, MM Lerch, GM Cavestro, RA Zuppardo, M Di Leo & 12 others PA Testoni, E Malecka-Panas, A Gasirowska, S Głuszek, P Bugert, A Szentesi, J Mössner, H Witt, P Michl, P Hégyi, M Scholz, J Rosendahl

Research output: Contribution to journalArticle

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. © 2018
Original languageEnglish
Pages (from-to)477-481
Number of pages5
JournalPancreatology
Volume18
Issue number5
DOIs
Publication statusPublished - 2018

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Pancreatitis
Odds Ratio
Chronic Pancreatitis
Confidence Intervals
Alcoholic Pancreatitis
Meta-Analysis
Gallstones
Freezing
Alcoholism
Single Nucleotide Polymorphism
Hospitalization
Genotype
Phenotype

Cite this

Weiss, FU., Hesselbarth, N., Párniczky, A., Mosztbacher, D., Lämmerhirt, F., Ruffert, C., ... Rosendahl, J. (2018). Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis. Pancreatology, 18(5), 477-481. https://doi.org/10.1016/j.pan.2018.05.486

Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis. / Weiss, FU; Hesselbarth, N; Párniczky, A; Mosztbacher, D; Lämmerhirt, F; Ruffert, C; Kovacs, P; Beer, S; Seltsam, K; Griesmann, H; Böhme, R; Kaune, T; Hollenbach, M; Schulz, HU; Simon, P; Mayerle, J; Lerch, MM; Cavestro, GM; Zuppardo, RA; Di Leo, M; Testoni, PA; Malecka-Panas, E; Gasirowska, A; Głuszek, S; Bugert, P; Szentesi, A; Mössner, J; Witt, H; Michl, P; Hégyi, P; Scholz, M; Rosendahl, J.

In: Pancreatology, Vol. 18, No. 5, 2018, p. 477-481.

Research output: Contribution to journalArticle

Weiss, FU, Hesselbarth, N, Párniczky, A, Mosztbacher, D, Lämmerhirt, F, Ruffert, C, Kovacs, P, Beer, S, Seltsam, K, Griesmann, H, Böhme, R, Kaune, T, Hollenbach, M, Schulz, HU, Simon, P, Mayerle, J, Lerch, MM, Cavestro, GM, Zuppardo, RA, Di Leo, M, Testoni, PA, Malecka-Panas, E, Gasirowska, A, Głuszek, S, Bugert, P, Szentesi, A, Mössner, J, Witt, H, Michl, P, Hégyi, P, Scholz, M & Rosendahl, J 2018, 'Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis', Pancreatology, vol. 18, no. 5, pp. 477-481. https://doi.org/10.1016/j.pan.2018.05.486
Weiss FU, Hesselbarth N, Párniczky A, Mosztbacher D, Lämmerhirt F, Ruffert C et al. Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis. Pancreatology. 2018;18(5):477-481. https://doi.org/10.1016/j.pan.2018.05.486
Weiss, FU ; Hesselbarth, N ; Párniczky, A ; Mosztbacher, D ; Lämmerhirt, F ; Ruffert, C ; Kovacs, P ; Beer, S ; Seltsam, K ; Griesmann, H ; Böhme, R ; Kaune, T ; Hollenbach, M ; Schulz, HU ; Simon, P ; Mayerle, J ; Lerch, MM ; Cavestro, GM ; Zuppardo, RA ; Di Leo, M ; Testoni, PA ; Malecka-Panas, E ; Gasirowska, A ; Głuszek, S ; Bugert, P ; Szentesi, A ; Mössner, J ; Witt, H ; Michl, P ; Hégyi, P ; Scholz, M ; Rosendahl, J. / Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis. In: Pancreatology. 2018 ; Vol. 18, No. 5. pp. 477-481.
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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. {\circledC} 2018",
author = "FU Weiss and N Hesselbarth and A P{\'a}rniczky and D Mosztbacher and F L{\"a}mmerhirt and C Ruffert and P Kovacs and S Beer and K Seltsam and H Griesmann and R B{\"o}hme and T Kaune and M Hollenbach and HU Schulz and P Simon and J Mayerle and MM Lerch and GM Cavestro and RA Zuppardo and {Di Leo}, M and PA Testoni and E Malecka-Panas and A Gasirowska and S Głuszek and P Bugert and A Szentesi and J M{\"o}ssner and H Witt and P Michl and P H{\'e}gyi and M Scholz and J Rosendahl",
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TY - JOUR

T1 - Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis

AU - Weiss, FU

AU - Hesselbarth, N

AU - Párniczky, A

AU - Mosztbacher, D

AU - Lämmerhirt, F

AU - Ruffert, C

AU - Kovacs, P

AU - Beer, S

AU - Seltsam, K

AU - Griesmann, H

AU - Böhme, R

AU - Kaune, T

AU - Hollenbach, M

AU - Schulz, HU

AU - Simon, P

AU - Mayerle, J

AU - Lerch, MM

AU - Cavestro, GM

AU - Zuppardo, RA

AU - Di Leo, M

AU - Testoni, PA

AU - Malecka-Panas, E

AU - Gasirowska, A

AU - Głuszek, S

AU - Bugert, P

AU - Szentesi, A

AU - Mössner, J

AU - Witt, H

AU - Michl, P

AU - Hégyi, P

AU - Scholz, M

AU - Rosendahl, J

PY - 2018

Y1 - 2018

N2 - 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. © 2018

AB - 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. © 2018

U2 - 10.1016/j.pan.2018.05.486

DO - 10.1016/j.pan.2018.05.486

M3 - Article

VL - 18

SP - 477

EP - 481

JO - Pancreatology

JF - Pancreatology

SN - 1424-3903

IS - 5

ER -