Γονοτυπικός-φαινοτυπικός συσχετισμός στην παγκρεατίτιδα

Abstract

Background: Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Monocyte chemotactic protein-1 (MCP-1) gene expression is altered by an A/G polymorphism (-2518), with the G allele increasing MCP-1 production. Obese patients appear to be at risk for complications of AP. APACHE-O score has been suggested to improve APACHE-II accuracy in predicting severe outcome in AP. Aims: Τo determine whether: 1) the MCP-1 −2518 A/G polymorphism affects the severity of AP, 2) if APACHE-O score adds any predictive value to APACHE-II score and 3) to test the hypothesis that obese patients are at increased risk of SAP because of a more intense inflammatory response to pancreatic injury. Methods: 102 consecutive AP patients and 116 controls were evaluated. The A/G genotype was evaluated by polymerase chain reaction amplification and DNA sequencing. MCP-1 serum levels were quantified using a fluorescence bead-based immunoassay. Receiver operating curves (ROC) for prediction of SAP were calculated using admission APACHE-II and APACHE-O scores. Binary logistic regression was performed to assess if obesity is a risk for SAP and to determine the clinical factors associated with severe disease. Serum levels of IL-6, MCP-1 and CRP as well as Ranson’s scores were compared between obese and non-obese patients. Results: Nineteen patients developed organ dysfunction and were classified as SAP. Patients with SAP had a significantly greater proportion of the G allele (86%) than did MAP patients (46%) (p 30, 28% of the subjects were obese. Admission APACHE-O (Area under the curve AUC: 0.895) and APACHE-II (AUC: 0.893) showed similar accuracy in predicting severe outcome. BMI>30 was identified as a significant risk for SAP (OR: 2.8, p=0.048) and mortality (OR: 11.2, p=0.022). CRP levels were significantly higher in obese AP patients (p=0.0001) as well as Ranson’s score (p=0.021). IL-6 and MCP-1 levels were higher in obese patients but did not reach statistical significance. Conclusions: MCP-1 −2518 G allele is a risk factor for severe AP. MCP-1 serum levels, measured early in the course of AP, appear to be an accurate predictor of severity of acute pancreatitis and death. Obesity is an independent risk for severe acute pancreatitis. Admission APACHE-O score is not more accurate than APACHE-II score. Our study results suggest that obesity increases the severity of AP by amplifying the immune response to injury.