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); = 0.008 and OR 5.33 (1.28–22.25); = 0.02), as well as higher prevalence of AP (OR 3.64 (0.89–14.92); = 0.07 and OR 11.90 (2.54–55.85); = 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.

中文翻译：

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多因素乳糜微粒血症综合征的急性胰腺炎风险取决于严重高甘油三酯血症的分子原因

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) 风险增加相关。重度hyperTG本质上主要是多基因的，要么是由TG相关代谢基因中存在杂合致病性变异（PV）引起，要么是由hyperTG易感基因中常见变异的积累引起。本研究旨在确定具有不同分子原因导致严重高甘油三酯血症的 MCS 患者发生 AP 的风险是否相似。这项研究包括 114 名 MCS 患者，他们接受了 TG 相关代谢基因 PV 和 hyperTG 易感基因 16 个单核苷酸多态性 (SNP) 的基因检测。计算加权 TG 多基因风险评分 (TG-PRS)。TG-PRS 分数 90% 用于定义高 TG-PRS。总体而言，66.7% 的患者患有多基因起源的严重高TG。仅具有 PV 的 MCS 患者以及同时具有 PV 和高 TG-PRS 的患者更容易出现最大 TG 浓度 40 mmol/L（OR 5.33 (1.55–18.36)；= 0.008 和 OR 5.33 (1.28–22.25)；= 0.02），并且与仅具有高 TG-PRS 的 MCS 患者相比，AP 患病率更高（OR 3.64 (0.89–14.92); = 0.07 和 OR 11.90 (2.54–55.85); = 0.002）。这是第一项研究表明，由高 TG-PRS 和 PV 引起的 MCS 与较高的 AP 风险相关，类似于单基因形式的严重高TG。这表明确定严重高甘油三酯的分子原因可能有助于对 MCS 中胰腺炎的风险进行分层。