Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada; Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
J Clin Lipidol. 2023 Sep-Oct;17(5):659-665. doi: 10.1016/j.jacl.2023.08.003. Epub 2023 Aug 7.
Biallelic pathogenic variants in APOA5 are an infrequent cause of familial chylomicronemia syndrome characterized by severe, refractory hypertriglyceridemia (HTG), and fasting plasma triglyceride (TG) >10 mmol/L (>875 mg/dL). The TG phenotype of heterozygous individuals with one copy of a pathogenic APOA5 variant is less familiar. We evaluated the longitudinal TG phenotype of individuals with a single pathogenic APOA5 variant allele.
Medically stable outpatients from Ontario, Canada were selected for study based on having: 1) a rare pathogenic APOA5 variant in a single allele; and 2) at least three serial fasting TG measurements obtained over >1.5 years of follow-up.
Seven patients were followed for a mean of 5.3 ± 3.7 years. Fasting TG levels varied widely both within and between patients. Three patients displayed at least one normal TG measurement (<2.0 mmol/L or <175 mg/dL). All patients displayed mild-to-moderate HTG (2 to 9.9 mmol/L or 175 to 875 mg/dL) at multiple time points. Five patients displayed at least one severe HTG measurement. 10%, 54%, and 36% of all TG measurements were in normal, mild-to-moderate, and severe HTG ranges, respectively.
Heterozygosity for pathogenic variants in APOA5 is associated with highly variable TG phenotypes both within and between patients. Heterozygosity confers susceptibility to elevated TG levels, with secondary factors likely modulating the phenotypic severity.
载脂蛋白 A5（APOA5）的双等位致病性变异是家族性乳糜微粒血症综合征的一个不常见病因，其特征为严重、难治性高甘油三酯血症（HTG），空腹血浆甘油三酯（TG）＞10mmol/L（＞875mg/dL）。具有一个致病性 APOA5 变异等位基因的杂合子个体的 TG 表型不太常见。我们评估了具有单拷贝致病性 APOA5 变异等位基因的个体的 TG 表型的纵向变化。
根据以下标准，从加拿大安大略省的稳定门诊患者中选择研究对象：1）单个等位基因中存在罕见的致病性 APOA5 变异；2）在＞1.5 年的随访中至少有 3 次连续的空腹 TG 测量值。
7 例患者的平均随访时间为 5.3±3.7 年。空腹 TG 水平在患者内和患者间均有很大差异。3 例患者至少有一次 TG 测量值正常（＜2.0mmol/L 或＜175mg/dL）。所有患者在多个时间点均表现出轻至中度 HTG（2 至 9.9mmol/L 或 175 至 875mg/dL）。5 例患者至少有一次严重 HTG 测量值。所有 TG 测量值中，分别有 10%、54%和 36%处于正常、轻至中度和严重 HTG 范围内。
APOA5 致病性变异的杂合性与患者内和患者间的 TG 表型均高度可变相关。杂合性导致 TG 水平升高易感性增加，继发性因素可能调节表型严重程度。
