Connections Between Genetics and Clinical Data: Role of MCP-1, CFTR, and SPINK-1 in the Setting of Acute, Acute Recurrent, and Chronic Pancreatitis.

Abstract OBJECTIVES: Acute, acute recurrent, and chronic pancreatitis are infl ammatory 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 fi brosis 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 signifi cantly higher in all patients affected by pancreatic infl ammatory diseases. Moreover, we found a signifi cant over-representation of the MCP-1G allele in ARP patients. We found a statistically signifi cant association of CFTR gene mutations with ARP, but not with CP. We did not fi nd a statistically signifi cant 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 fi ve 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 infl ammatory response, clinical features, and exogenous factors.