Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis
Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis
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DOI：
10.1016/j.pan.2018.05.486
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发表时间：
2018-07-01
期刊：
影响因子：
3.6
通讯作者：
Rosendahl, Jonas
中科院分区：
文献类型：
--
作者：
Weiss, Frank Ulrich;Hesselbarth, Nico;Rosendahl, Jonas
背景/目的：急性胰腺炎（AP）是最常见的胃肠道疾病之一，经常需要住院治疗。常见的病因是胆结石和酗酒。与慢性胰腺炎（CP）相比，很少有可靠的遗传关联。在这里，我们分析了CLDN 2-MORC 4和PRSS 1-PRSS 2基因座中增加AP复发和CP风险的常见变异是否与AP.Methods相关：我们用熔解曲线分析筛选了1462名AP患者和3999名对照，以分析SNPs rsl 0273639（PRSS 1-PRSS 2）、rs7057398（RIPS 1）和rsl 2688220（MORC 4）。对整个组、病因和性别亚组进行计算。为了检查基因型-表型关系，我们进行了几项荟萃分析。所有AP患者的荟萃分析显示，（p值< 0.05）rs 10273639的相关性（比值比（OR）0.88，95%置信区间（CI）0.81-0.97，p值0.01），rs7057398（OR 1.27，95% CI 1.07-1.5，p值0.005）和rs 12688220（OR 1.32，95% CI 1.12-1.56，p值0.001）。对于不同的病因组，rs 10273639显示出显著相关性。（OR 0.76，95% CI 0.63-0.92，p值0.005），rs7057398（OR 1.43，95% CI 1.07-1.92，p值0.02）和rs 12688220（OR 1.44，95% CI 1.07-1.93，p值0.02）。结论：CP风险变异与不同AP病因的相关性在酒精性AP组中最强，可能暗示酒精性AP和CP之间最有可能存在共同的病理机制。(C)2018年IAP和EPC。Elsevier B. V.出版，保留所有权利。
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 rsl0273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rsl2688220 (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. (C) 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.