Department of Clinical Science, University of Parma, Italy.
Am J Gastroenterol. 2010 Jan;105(1):199-206. doi: 10.1038/ajg.2009.611. Epub 2009 Oct 20.
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.
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.
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.
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.
急性胰腺炎、复发性急性胰腺炎和慢性胰腺炎是具有多因素发病机制的炎症性疾病。遗传突变和多态性与胰腺炎有关。本研究旨在探讨囊性纤维化跨膜电导调节因子（CFTR）和丝氨酸蛋白酶抑制剂 Kazal 型 1（SPINK-1）基因突变以及单核细胞趋化蛋白 1（MCP-1）-2518A/G 多态性与急性胰腺炎（AP）、复发性急性胰腺炎（ARP）和慢性胰腺炎（CP）的相关性，并将遗传背景与这三种疾病的临床表型相关联。
连续纳入 118 例 AP、64 例 ARP、142 例 CP 患者和 88 例正常对照者。采用酶联免疫吸附试验检测 MCP-1 血清水平。采用 PCR-限制性片段长度多态性分析 MCP-1-2518 多态性和 SPINK-1 N34S 基因突变。必要时进行序列分析。采用多重 DNA 检测分析 CP 和 ARP 患者的 33 种 CFTR 突变。
所有患有胰腺炎症性疾病的患者的血清 MCP-1 水平均显著升高。此外，我们发现 ARP 患者中 MCP-1G 等位基因的表达显著增加。我们发现 CFTR 基因突变与 ARP 显著相关，但与 CP 无关。我们没有发现 ARP 或 CP 与 SPINK-1 N34S 基因突变之间存在统计学显著关联。有趣的是，64 例 ARP 患者中有 39 例（61%）至少携带一种遗传突变和/或多态性。64 例 ARP 患者中有 5 例存在胰腺分裂，其中 5 例也携带 G 等位基因。
需要分析广泛的潜在易感性变异，以支持对胰腺炎中基因和环境影响的建模。因此，除了基因突变外，还必须考虑这些突变存在的背景。在胰腺炎中，这种背景包括炎症反应、临床特征和外源性因素。
