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

Weiss, Frank Ulrich; Hesselbarth, Nico; Párniczky, Andrea; Mosztbacher, Dóra; Lämmerhirt, Felix; Ruffert, Claudia; Kovacs, Peter; Beer, Sebastian; Seltsam, Katharina; Griesmann, Heidi; Böhme, Richard; Kaune, Tom; Hollenbach, Marcus; Schulz, Hans–Ulrich; Simon, Péter; Mayerle, Julia; Lerch, Markus M.; Cavestro, Giulia Martina; Zuppardo, Raffaella Alessia; Leo, Milena Di; Testoni, Pier Alberto; Małecka‐Panas, Ewa; Gasirowska, Anita; Głuszek, Stanisław; Bugert, Peter; Szentesi, Andrea; Mössner, Joachim; Witt, Heiko; Michl, Patrick; Hegyi, Péter; Scholz, Markus; Rosendahl, Jonas

doi:10.1016/j.pan.2018.05.486

Cited by 16 publications

(14 citation statements)

References 20 publications

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“…In our study, there was no association between polymorphism at rs10273639 and PEP and the proportion of CC : CT : TT genotypes was 65% : 32.5% : 2.5% versus 72% : 27% : 1% in case and control, respectively. In our study population, majority of patients in both groups carry CC genotypes and TT genotype was relatively lower when compared with the study from Europe [ 4 , 5 ], which had proportions of TT genotypes in either acute pancreatitis, alcoholic chronic hepatitis, or control groups ranged from 9 to 18%. The association between polymorphisms at rs10273639 and acute pancreatitis was not universally identified across European countries in the previous study [ 5 ]; the association was found in Germany and Hungary, but not Italy and Poland.…”

Section: Discussioncontrasting

confidence: 52%

“…In our study population, majority of patients in both groups carry CC genotypes and TT genotype was relatively lower when compared with the study from Europe [ 4 , 5 ], which had proportions of TT genotypes in either acute pancreatitis, alcoholic chronic hepatitis, or control groups ranged from 9 to 18%. The association between polymorphisms at rs10273639 and acute pancreatitis was not universally identified across European countries in the previous study [ 5 ]; the association was found in Germany and Hungary, but not Italy and Poland. Additionally, the study from India [ 13 ] demonstrated the proportion of TT genotypes in idiopathic recurrent pancreatitis, chronic pancreatitis, and control of 50%, 51%, and 54%, respectively.…”

Section: Discussioncontrasting

confidence: 52%

“…However, T ( TT ) genotypes associate with atypical localization of claudin-2 to the basolateral membrane of acinar cells [ 3 ] and associate with the development of pancreatitis [ 3 , 4 ]. Prior studies demonstrated the association between polymorphism at rs12688220 and all-cause acute pancreatitis, including 56 patients of PEP [ 5 ]. However, in subgroup analysis, the associations were presented only in alcoholic acute pancreatitis and patients in Italy and Poland, not Germany and Hungary [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…Genetic susceptibility was proven to be a predisposing factor in alcoholic pancreatitis by a mechanism of lowering threshold of susceptibility to develop pancreatitis [ 3 , 4 ]. The polymorphisms at PRSS1-PRSS2 rs10273739 , which influence trypsinogen expression, and MORC4 rs12688220 , which associate with atypical localization of cludin-2 in pancreatic acinar cells, are associated with acute pancreatitis [ 5 ], related recurrent acute pancreatitis, and chronic pancreatitis [ 3 , 4 ]. We hypothesized that patients with high susceptibility to pancreatitis might have higher incidence of PEP that those without these genetic risk factors.…”

Section: Introductionmentioning

confidence: 99%

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The Polymorphisms at PRSS1-PRSS2 and MORC4 Loci and the Risk of Post-ERCP Pancreatitis

Angsuwatcharakon

Sodsai

Rerknimitr

et al. 2018

Gastroenterology Research and Practice

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Background and Aim The risks of post-ERCP pancreatitis (PEP) are identified as patient- and procedure-related factors. However, the genetic contribution for PEP is still unclear. Recent data show that the polymorphisms of PRSS1-PRSS2 (rs10273639) and MORC4 (rs12688220) are associated with recurrent acute pancreatitis and chronic pancreatitis. We aim to evaluate the association between these polymorphisms and post-ERCP pancreatitis in order to improve better prognosis and better care for these patients. Methods This is a retrospective, case-control study which includes 49 cases and 97 controls that are age-, procedure-, and risk of PEP-matched with the cases in 1 : 2 fashion. The PEP was diagnosed and graded for severity according to the standard consensus, and the risk factors of PEP were identified according to the ESGE guideline. Polymorphisms at rs10273639 and rs12688220 were evaluated by TaqMan technique and were identified in 133 (40 cases and 93 controls) and 146 patients, respectively. Results The demographic data between 2 groups are not significantly different. The genotype frequencies of PRSS1-PRSS2 (TT, TC, and CC) are 26, 13, and 1 vs. 67, 25, and 1 in cases and controls, respectively (p = 0.642). The genotype frequencies of MORC4 in female (TT, TC, and CC) are 8, 23, and 5 vs. 12, 26, and 21 in cases and controls, respectively (p = 0.071). The genotype frequencies of MORC4 in male (T and C) are 5 and 8 vs. 21 and 17 in cases and controls, respectively (p = 0.468). The allelic frequencies of MORC4 in combination of both genders (T, C) are 44 and 41 vs. 71 and 84 in cases and control, respectively (p = 0.431). In PEP cases, the allelic frequencies of PRSS1-PRSS2 (T and C) are 59 and 13 vs. 6 and 2 in mild and moderate/severe cases, respectively (p = 0.633). The allelic frequencies of MORC4 (T and C) are 38 and 39 vs. 4 and 4 in mild and moderate/severe cases, respectively (p = 0.972). Conclusion Polymorphisms at PRSS1-PRSS2 and MORC4 are not associated with the risk or severity of post-ERCP pancreatitis.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Polymorphisms at PRSS1-PRSS2 and MORC4 Loci and the Risk of Post-ERCP Pancreatitis

Angsuwatcharakon

Sodsai

Rerknimitr

et al. 2018

Gastroenterology Research and Practice

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“…Significant association with pancreatitis has also been demonstrated for sequence variants in CASR [54], CLDN2 [55-57], and CEL [58, 59]. Preliminary reports which await further validation include CTSB [60], MYO9B [61], and UBR1 [62], or the association of an increased pancreatitis risk with ABO blood group and the so-called “secretor status,” which is determined by a mutation of the fucosyltransferase gene FUT2 [29, 63].…”

Section: Recurrent Acute and Chronic Pancreatitis: Distinction And Etmentioning

confidence: 99%

Etiology and Risk Factors of Acute and Chronic Pancreatitis

Weiss

Laemmerhirt

Lerch³

2019

Visc Med

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Based on the recognition of common etiological and genetic risk factors, acute and chronic pancreatitis are increasingly regarded as a continuum of the same disease, with a significant overlap of clinical manifestations and phenotypes but distinct morphological and imaging appearances. Recent population-based and cohort studies have found that tobacco smoke conveys a greater risk than immoderate alcohol consumption for the development of chronic pancreatitis, and hypertriglyceridemia has been identified as a risk factor for acute pancreatitis – even when plasma levels are only mildly elevated. Hereditary pancreatitis, in its autosomal dominant form, is associated with mutations in the cationic trypsinogen gene (PRSS1), whereas a number of germline variations in other genes have been found to represent risk factors for chronic as well as acute pancreatitis. For now, most of these involve the pancreatic digestive protease/antiprotease system. Oftentimes, affected patients are burdened with multiple or accumulating risk factors, and genetic traits when combined with environmental toxins compound the chance of developing the disease. Determining the underlying etiology of pancreatitis is worth the effort since formerly intractable varieties such as autoimmune pancreatitis are now becoming increasingly treatable, and subtype-specific therapeutic modalities may become available.

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Acute Pancreatitis

Barkin¹,

Barkin²

2021

Clinical Pancreatology for Practising Gastroenterologists and Surgeons

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

Cited by 16 publications

References 20 publications

The Polymorphisms at PRSS1-PRSS2 and MORC4 Loci and the Risk of Post-ERCP Pancreatitis

The Polymorphisms at PRSS1-PRSS2 and MORC4 Loci and the Risk of Post-ERCP Pancreatitis

Etiology and Risk Factors of Acute and Chronic Pancreatitis

Acute Pancreatitis

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