Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada; Department of Medicine, Division of Endocrinology, Université de Montréal, Montréal, Québec, Canada.
Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada.
Atherosclerosis. 2024 May;392:117489. doi: 10.1016/j.atherosclerosis.2024.117489. Epub 2024 Feb 27.
Multifactorial chylomicronemia syndrome (MCS) is a severe form of hypertriglyceridemia (hyperTG) associated with an increased risk of acute pancreatitis (AP). Severe hyperTG is mainly polygenic in nature, either caused by the presence of heterozygous pathogenic variants (PVs) in TG-related metabolism genes or by accumulation of common variants in hyperTG susceptibility genes. This study aims to determine if the risk of AP is similar amongst MCS patients with different molecular causes of severe hyperTG.
This study included 114 MCS patients who underwent genetic testing for PVs in TG-related metabolism genes and 16 single nucleotide polymorphisms (SNPs) in hyperTG susceptibility genes. A weighted TG-polygenic risk score (TG-PRS) was calculated. A TG-PRS score ≥ 90th percentile was used to define a high TG-PRS.
Overall, 66.7% of patients had severe hyperTG of polygenic origin. MCS patients with only a PV and those with both a PV and high TG-PRS were more prone to have maximal TG concentration ≥ 40 mmol/L (OR 5.33 (1.55-18.36); p = 0.008 and OR 5.33 (1.28-22.25); p = 0.02), as well as higher prevalence of AP (OR 3.64 (0.89-14.92); p = 0.07 and OR 11.90 (2.54-55.85); p = 0.002) compared to MCS patients with high TG-PRS alone.
This is the first study to show that MCS caused by a high TG-PRS and a PV is associated with higher risk of AP, similar to what is seen in the monogenic form of severe hyperTG. This suggests that determining the molecular cause of severe hyperTG could be useful to stratify the risk of pancreatitis in MCS.
多因素乳糜微粒血症综合征（MCS）是一种严重的高甘油三酯血症（hyperTG），与急性胰腺炎（AP）风险增加有关。严重的高甘油三酯血症主要是多基因性质的，要么是由于甘油三酯代谢基因中的杂合致病性变异（PV）的存在，要么是由于高甘油三酯易感性基因中的常见变异的积累。本研究旨在确定不同严重高甘油三酯血症分子病因的 MCS 患者的 AP 风险是否相似。
本研究纳入了 114 名接受甘油三酯代谢基因 PV 检测和 16 个高甘油三酯易感性基因单核苷酸多态性（SNP）检测的 MCS 患者。计算了甘油三酯多基因风险评分（TG-PRS）。TG-PRS 评分≥90 百分位数定义为高 TG-PRS。
总体而言，66.7%的患者存在多基因来源的严重高甘油三酯血症。仅存在 PV 和同时存在 PV 和高 TG-PRS 的 MCS 患者，其最大甘油三酯浓度≥40mmol/L 的几率更高（OR 5.33（1.55-18.36）；p=0.008 和 OR 5.33（1.28-22.25）；p=0.02），且 AP 的患病率更高（OR 3.64（0.89-14.92）；p=0.07 和 OR 11.90（2.54-55.85）；p=0.002）。与仅存在高 TG-PRS 的 MCS 患者相比。
这是第一项表明 MCS 由高 TG-PRS 和 PV 引起，与单基因形式的严重高甘油三酯血症一样，AP 风险更高的研究。这表明，确定严重高甘油三酯血症的分子病因可能有助于对 MCS 的胰腺炎风险进行分层。
