May 15, 2020Open Access
View Full PaperDissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia
Key Result
Familial chylomicronemia syndrome was discriminated from multifactorial chylomicronemia by specific clinical variables (AUC ≥0.7) and exhibited 63 specific differentially expressed gene probes.
Study Design
Type
Observational (n=425)
Structured PICO
What are the clinical and gene expression signatures that differentiate familial chylomicronemia syndrome from multifactorial chylomicronemia?
P
Population
410 patients with familial or multifactorial chylomicronemia and 15 normolipidemic controls evaluated for clinical and gene expression profiles.
C
Comparator
Multifactorial chylomicronemia (MCM) patients and normolipidemic controls
O
Outcome
Clinical and gene expression signatures discriminating FCS from MCMsurrogate
Familial chylomicronemia syndrome and multifactorial chylomicronemia exhibit distinct clinical and gene expression signatures, which may aid in differential diagnosis and the identification of novel therapeutic targets.
Main Result
Effect estimate: AUC ≥0.7
Abstract
Abstract Familial chylomicronemia syndrome (FCS) is a rare disorder associated with chylomicronemia (CM) and an increased risk of pancreatitis. Most individuals with CM do not have FCS but exhibit multifactorial CM (MCM), which differs from FCS in terms of risk and disease management. This study aimed to investigate clinical and gene expression profiles of FCS and MCM patients. Anthropometrics, clinical, and biochemical variables were analyzed in 57 FCS and 353 MCM patients. Gene expression analyses were performed in a subsample of 19 FCS, 28 MCM, and 15 normolipidemic controls. Receiver operating characteristic (ROC) curve analyses were performed to analyze the capacity of variables to discriminate FCS from MCM. Sustained fasting triglycerides ≥20 mmol/L (15 mmol/L with eruptive xanthomas), history of pancreatitis, poor response to fibrates, diagnosis of CM at childhood, body mass index 22 kg/m2, and delipidated apolipoprotein B or glycerol levels 0.9 g/L and 0.05 mmol/L, respectively, had an area under the ROC curve ≥0.7. Gene expression analyses identified 142 probes differentially expressed in FCS and 32 in MCM compared with controls. Among them, 13 probes are shared between FCS and MCM; 63 are specific to FCS and 2 to MCM. Most FCS-specific or shared biomarkers are involved in inflammatory, immune, circadian, postprandial metabolism, signaling, docking systems, or receptor-mediated clearance mechanisms. This study reveals differential signatures of FCS and MCM. It opens the door to the identification of key mechanisms of CM expression and potential targets for the development of new treatments.