Tremblay Karine, Gaudet Daniel, Khoury Etienne, Brisson Diane
Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, Quebec, Canada.
Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean, Saguenay, Quebec, Canada.
J Endocr Soc. 2020 May 15;4(6):bvaa056. doi: 10.1210/jendso/bvaa056. eCollection 2020 Jun 1.
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/m, 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.
家族性乳糜微粒血症综合征（FCS）是一种罕见的疾病，与乳糜微粒血症（CM）相关，且胰腺炎风险增加。大多数CM患者没有FCS，但表现为多因素性CM（MCM），MCM在风险和疾病管理方面与FCS不同。本研究旨在调查FCS和MCM患者的临床和基因表达谱。对57例FCS患者和353例MCM患者进行了人体测量学、临床和生化变量分析。在19例FCS、28例MCM和15例正常血脂对照的子样本中进行了基因表达分析。进行了受试者工作特征（ROC）曲线分析，以分析变量区分FCS和MCM的能力。持续空腹甘油三酯≥20 mmol/L（有疹性黄瘤时>15 mmol/L）、胰腺炎病史、对贝特类药物反应不佳、儿童期诊断为CM、体重指数<22 kg/m²，以及脱脂载脂蛋白B或甘油水平分别<0.9 g/L和<0.05 mmol/L，ROC曲线下面积≥0.7。基因表达分析确定，与对照组相比，FCS中有142个探针差异表达，MCM中有32个探针差异表达。其中，13个探针在FCS和MCM之间共享；63个是FCS特有的，2个是MCM特有的。大多数FCS特异性或共享的生物标志物参与炎症、免疫、昼夜节律、餐后代谢、信号传导、对接系统或受体介导的清除机制。本研究揭示了FCS和MCM的不同特征。它为识别CM表达的关键机制以及开发新治疗方法的潜在靶点打开了大门。
