Connections Between Genetics and Clinical Data: Role of MCP-1, CFTR, and SPINK-1 in the Setting of Acute, Acute Recurrent, and Chronic Pancreatitis
Connections Between Genetics and Clinical Data: Role of MCP-1, CFTR, and SPINK-1 in the Setting of Acute, Acute Recurrent, and Chronic Pancreatitis
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DOI：
10.1038/ajg.2009.611
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发表时间：
2010-01-01
影响因子：
9.8
通讯作者：
Di Mario, Francesco
中科院分区：
文献类型：
--
作者：
Cavestro, Giulia Martina;Zuppardo, Raffaella Alessia;Di Mario, Francesco
急性胰腺炎、急性复发性胰腺炎和慢性胰腺炎是具有多因素致病机制的炎性疾病。基因突变和多态性与胰腺炎相关。本研究的目的是探讨囊性纤维化跨膜传导调节因子（CFTR）和丝氨酸蛋白酶抑制剂Kazal 1型之间的关系。（SPINK- 1）基因突变和单核细胞趋化蛋白1（MCP-1）-2518A/G多态性与急性胰腺炎（AP）、急性复发性胰腺炎（阿普）和慢性胰腺炎（CP），方法：连续入选118例AP、64例阿普、142例CP患者和88例正常对照。我们用酶联免疫吸附试验分析MCP-1血清水平。采用PCR-限制性片段长度多态性分析方法检测MCP-1和SPINK-1 N34 S基因突变的-2518多态性。必要时进行序列分析。使用多重DNA检测分析了CP和阿普患者的33个CFTR突变。结果：所有胰腺炎性疾病患者的血清MCP-1水平均显著升高。此外，我们发现阿普患者中MCP-1G等位基因的显著过度表达。我们发现CFTR基因突变与阿普有统计学意义的相关性，但与CP无关。我们没有发现阿普或CP与N34 S SPINK- 1基因突变的统计学显著相关性。有趣的是，64例阿普患者中有39例（61%）携带至少一种基因突变和/或多态性。五个64阿普患者胰腺分裂，这五个也进行了G等位基因。结论：一个全面的潜在的易感性变异的分析是必要的，以支持建模的基因和环境在胰腺炎的影响。因此，除了基因突变之外，必须考虑这些突变存在的背景。在胰腺炎中，背景包括炎症反应、临床特征和外源性因素。
OBJECTIVES: Acute, acute recurrent, and chronic pancreatitis are inflammatory diseases with multifactorial pathogenic mechanisms. Genetic mutations and polymorphisms have been correlated with pancreatitis. The aim of this study was to investigate the association of cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK- 1) gene mutations and monocyte chemoattractant protein 1 (MCP-1) -2518A/G polymorphism with acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP), and to associate genetic backgrounds with clinical phenotype in these three conditions.METHODS: One hundred eighteen AP, 64 ARP, 142 CP patients, and 88 normal controls were enrolled consecutively. We analyzed MCP-1 serum levels using enzyme-linked immunosorbent assay. Polymorphism -2518 of MCP-1 and SPINK-1 N34S gene mutations were determined by PCR restriction-fragment length polymorphism. Sequence analysis was performed when necessary. Thirty-three CFTR mutations were analyzed in CP and ARP patients using multiplex DNA testing.RESULTS: Serum MCP-1 levels were significantly higher in all patients affected by pancreatic inflammatory diseases. Moreover, we found a significant over-representation of the MCP-1G allele in ARP patients. We found a statistically significant association of CFTR gene mutations with ARP, but not with CP. We did not find a statistically significant association of ARP or CP with the N34S SPINK- 1 gene mutation. Interestingly, 39 of 64 ARP patients (61%) carried at least one genetic mutation and/or polymorphism. Five of 64 ARP patients had pancreas divisum and four of these five also carried the G allele.CONCLUSIONS: Analysis of a comprehensive range of potential susceptibility variants is needed to support modeling of the effects of genes and environment in pancreatitis. As such, beyond gene mutations, the context within which those mutations exist must be considered. In pancreatitis the context includes the inflammatory response, clinical features, and exogenous factors.