Abstract：
BACKGROUND: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines.
METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced.
RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls.
CONCLUSIONS: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.
METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced.
RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls.
CONCLUSIONS: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.
摘要：
背景：在炎症性肠病（IBD）患者中硫嘌呤类药物导致胰腺炎的危险因素尚未明确。
目的：我们的目的是评估用硫嘌呤治疗的IBD患者发生胰腺炎的预测的药物遗传风险。
方法：我们在一项队列研究中进行了急性胰腺炎事件的观察性药物遗传学研究，该研究来自GETECCU前瞻性维持的ENEIDA注册生物库，对接受硫嘌呤治疗的IBD患者进行了研究。获得样品和CASR，CEL,CFTR,CDLN2,CTRC,SPINK1、CPA1和PRSS1基因，根据他们与胰腺炎的已知关联进行选择，已完全测序。
结果：纳入95例病例和105例对照，57%是女性。诊断为胰腺炎的中位年龄为39岁。我们确定了81种良性变异（病例50种，对照67种）和总共35种不同的罕见致病性和未知意义的变异（CEL中的10种，21在CFTR中，1在CDLN2中，3在CPA1中）。没有病例或对照在CASR内携带胰腺炎易感变异，CPA1、PRSS1和SPINK1基因，也不是致病性CFTR突变。在CDLN和CPA1基因中检测到四种未知意义的不同变异；其中一种是在单个胰腺炎患者的CDLN基因中，3在5个对照的CPA1基因中。在分析检测到的变异后，病例与对照组之间无显著差异.
结论：在IBD患者中，已知导致胰腺炎的基因似乎不参与硫嘌呤相关胰腺炎的发病。
目的：我们的目的是评估用硫嘌呤治疗的IBD患者发生胰腺炎的预测的药物遗传风险。
方法：我们在一项队列研究中进行了急性胰腺炎事件的观察性药物遗传学研究，该研究来自GETECCU前瞻性维持的ENEIDA注册生物库，对接受硫嘌呤治疗的IBD患者进行了研究。获得样品和CASR，CEL,CFTR,CDLN2,CTRC,SPINK1、CPA1和PRSS1基因，根据他们与胰腺炎的已知关联进行选择，已完全测序。
结果：纳入95例病例和105例对照，57%是女性。诊断为胰腺炎的中位年龄为39岁。我们确定了81种良性变异（病例50种，对照67种）和总共35种不同的罕见致病性和未知意义的变异（CEL中的10种，21在CFTR中，1在CDLN2中，3在CPA1中）。没有病例或对照在CASR内携带胰腺炎易感变异，CPA1、PRSS1和SPINK1基因，也不是致病性CFTR突变。在CDLN和CPA1基因中检测到四种未知意义的不同变异；其中一种是在单个胰腺炎患者的CDLN基因中，3在5个对照的CPA1基因中。在分析检测到的变异后，病例与对照组之间无显著差异.
结论：在IBD患者中，已知导致胰腺炎的基因似乎不参与硫嘌呤相关胰腺炎的发病。
