Nijmeijer Rian M, van Santvoort Hjalmar C, Zhernakova Alexandra, Teller Steffen, Scheiber Jonas A, de Kovel Carolien G, Besselink Marc G H, Visser Jeroen T J, Lutgendorff Femke, Bollen Thomas L, Boermeester Marja A, Rijkers Ger T, Weiss Frank U, Mayerle Julia, Lerch Markus M, Gooszen Hein G, Akkermans Louis M A, Wijmenga Cisca
Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
Complex Genetics Group, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
PLoS One. 2013 Dec 30;8(12):e85870. doi: 10.1371/journal.pone.0085870. eCollection 2013.
Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis.
Five single nucleotide polymorphisms (SNPs) in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls.
Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p < 0.05). Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR) 1.94, 95% confidence interval (95% CI) 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53). SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology.
Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2.
黏膜屏障受损在急性胰腺炎的病理生理学中起重要作用。肌球蛋白IXB（MYO9B）基因以及两个紧密连接衔接蛋白基因PARD3和MAGI2与胃肠道通透性有关。这些基因的常见变异与乳糜泻和炎症性肠病相关，这两种疾病中肠道通透性也起作用。我们研究了MYO9B、PARD3和MAGI2的基因变异与急性胰腺炎的关联。
在一个由387例急性胰腺炎患者和800多名对照组成的荷兰队列以及一个由235例患者和250例对照组成的德国队列中，研究了MYO9B中的5个单核苷酸多态性（SNP）、PARD3中的2个SNP以及MAGI2中的3个SNP。
在荷兰队列中观察到与MYO9B和PARD3的关联，但在德国队列中只有MYO9B中的一个SNP和MAGI2中的一个SNP显示出关联（p < 0.05）。对合并队列的联合分析表明，在进行多重检验校正后，只有MYO9B中的两个SNP仍然具有关联性（rs7259292，p = 0.0031，比值比（OR）1.94，95%置信区间（95%CI）1.35 - 2.78；rs1545620，p = 0.0006，OR 1.33，95%CI 1.16 - 1.53）。SNP rs1545620是一个非同义SNP，之前怀疑其对溃疡性结肠炎有影响。没有一个SNP与疾病严重程度或病因相关。
MYO9B的变异可能与急性胰腺炎有关，但我们没有发现PARD3或MAGI2参与其中的证据。
