TY - JOUR
T1 - Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis
AU - Weiss, Frank Ulrich
AU - Hesselbarth, Nico
AU - Párniczky, Andrea
AU - Mosztbacher, Dora
AU - Lämmerhirt, Felix
AU - Ruffert, Claudia
AU - Kovacs, Peter
AU - Beer, Sebastian
AU - Seltsam, Katharina
AU - Griesmann, Heidi
AU - Böhme, Richard
AU - Kaune, Tom
AU - Hollenbach, Marcus
AU - Schulz, Hans Ulrich
AU - Simon, Peter
AU - Mayerle, Julia
AU - Lerch, Markus M.
AU - Cavestro, Giulia Martina
AU - Zuppardo, Raffaella Alessia
AU - Di Leo, Milena
AU - Testoni, Pier Alberto
AU - Malecka-Panas, Ewa
AU - Gasirowska, Anita
AU - Głuszek, Stanislaw
AU - Bugert, Peter
AU - Szentesi, Andrea
AU - Mössner, Joachim
AU - Witt, Heiko
AU - Michl, Patrick
AU - Hégyi, Peter
AU - Scholz, Markus
AU - Rosendahl, Jonas
N1 - Publisher Copyright:
© 2018 IAP and EPC
PY - 2018/7
Y1 - 2018/7
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.
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.
KW - Acute pancreatitis
KW - Genetics
KW - Risk factors
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85048543996&partnerID=8YFLogxK
U2 - 10.1016/j.pan.2018.05.486
DO - 10.1016/j.pan.2018.05.486
M3 - Article
C2 - 29884332
AN - SCOPUS:85048543996
SN - 1424-3903
VL - 18
SP - 477
EP - 481
JO - Pancreatology
JF - Pancreatology
IS - 5
ER -