Gene expression profiles of recurrent acute pancreatitis risk in patients with sustained chylomicronemia

Abstract

A fasting triglyceridemia >10 mmol/L is associated with chylomicronemia (CM) and an increased recurrent acute pancreatitis (RAP) risk. The number of pancreatitis episodes varies significantly between patients with CM. The objective of this study was to investigate gene expression profiles of RAP in patients with CM. A total of 47 CM subjects participated in this study. Prior to the analyses, all patients were divided into three groups covering a wide spectrum of RAP: 0 (n = 21), 1-3 (n = 10) or >4 (n = 16) pancreatitis episodes. Gene expression profiles were compared to those of 15 healthy normolipidemic controls. Differential expression moderated T-tests between studied groups were performed using a linear model of the Bioconductor package Limma. The False discovery rate was controlled using the Benjamini-Hochberg procedure. At a pvalue <0.01, a false discovery rate of 5% and a >2-fold change expression significance levels, a set of 41 probes have been found differentially expressed in CM subjects with no pancreatitis, 103 in the CM group with 1 to 3 pancreatitis, and 94 in the group with ≥4 pancreatitis compared to healthy controls. Of the identified annotated probes, 14 are shared by all CM groups; 3 are specific to CM with no pancreatitis; 11 are specific to CM with 1 to 3 pancreatitis, and 17 are specific to CM with ≥4 pancreatitis. Most of the annotated biomarkers are involved in inflammatory, immune, lipoprotein kinetics or signalling biological pathways. These results reveal gene expression signatures of RAP in patients with CM.

Non-Alcoholic Fatty Liver in Patients with Chylomicronemia

“…Results of this study suggest that there is a negative correlation between liver fat accumulation and acute pancreatitis risk in presence of chylomicronemia, suggesting that if more TG accumulates in the liver (NAFLD), less is available to contribute to the pancreatic fat pad (NAFPD) and associated pro-inflammatory environment, while the opposite could be observed for other patients. Gene expression signatures and clinical profiles of pancreatitis risk among chylomicronemic patients have been recently identified and several differentially expressed genes are associated with inflammation and fat metabolism [41]. Stratification for NAFLD and body fat distribution for these gene and clinical signatures are currently ongoing by using dynamic positron emission tomography (PET) technology to assess the body fat distribution in patients with chylomicronemia with or without RAP.…”