Abstract：
BACKGROUND: This study aims to show the clinical and biochemical features in patients with severe hypertriglyceridemia (HTG) associated with rare variants in the apolipoprotein A-V (APOA5) gene.
METHODS: Demographics, blood lipid levels, body mass index (BMI) and APOA5 mutation subtypes were collected from the endocrinology clinic registry and analyzed for a retrospective cohort study of ten patients with severe HTG and APOA5 gene variants.
RESULTS: Of the 10 cases, four were female, and six were male. The median age was 45.0 years (min-max: 21-60 years), the median triglyceride was 2429.5 mg/dL (27.5 mmol/L) (min-max: 1351-4087 mg/dL, 15.3-46.2 mmol/L), and the mean BMI was calculated as 30.4 ± 4.4 kg/m2 (min-max: 24.9-41.0 kg/m2). Four cases had diabetes mellitus (DM); two were on intensive insulin therapy, and two were on basal insulin therapy. The mean hemoglobin A1c was 9.2 ± 1.2 % (min-max: 8.3-11.0 %). Among the study group, eight different APOA5 gene mutations were detected. These variants were heterozygous in 2 patients and homozygous (bi-allelic) in 8 patients. One patient was homozygous for APOA5 p.Ser19Trp, a relatively common polymorphism that is a risk variant for HTG.
CONCLUSIONS: We report a cohort of patients with biallelic and single copy APOA5 variants, who were diagnosed later in life. Most had secondary factors, such as DM or obesity with increased BMI. Most rare APOA5 variants found in our patients were of uncertain significance. Our results add to the growing evidence that rare variants in certain candidate genes may predispose to developing HTG, together with secondary factors such as obesity. The genetic basis of HTG in many other patients is still unknown and remains the subject of further investigation.
METHODS: Demographics, blood lipid levels, body mass index (BMI) and APOA5 mutation subtypes were collected from the endocrinology clinic registry and analyzed for a retrospective cohort study of ten patients with severe HTG and APOA5 gene variants.
RESULTS: Of the 10 cases, four were female, and six were male. The median age was 45.0 years (min-max: 21-60 years), the median triglyceride was 2429.5 mg/dL (27.5 mmol/L) (min-max: 1351-4087 mg/dL, 15.3-46.2 mmol/L), and the mean BMI was calculated as 30.4 ± 4.4 kg/m2 (min-max: 24.9-41.0 kg/m2). Four cases had diabetes mellitus (DM); two were on intensive insulin therapy, and two were on basal insulin therapy. The mean hemoglobin A1c was 9.2 ± 1.2 % (min-max: 8.3-11.0 %). Among the study group, eight different APOA5 gene mutations were detected. These variants were heterozygous in 2 patients and homozygous (bi-allelic) in 8 patients. One patient was homozygous for APOA5 p.Ser19Trp, a relatively common polymorphism that is a risk variant for HTG.
CONCLUSIONS: We report a cohort of patients with biallelic and single copy APOA5 variants, who were diagnosed later in life. Most had secondary factors, such as DM or obesity with increased BMI. Most rare APOA5 variants found in our patients were of uncertain significance. Our results add to the growing evidence that rare variants in certain candidate genes may predispose to developing HTG, together with secondary factors such as obesity. The genetic basis of HTG in many other patients is still unknown and remains the subject of further investigation.
摘要：
背景：本研究旨在显示与载脂蛋白A-V（APOA5）基因罕见变异相关的重度高甘油三酯血症（HTG）患者的临床和生化特征。
方法：人口统计，血脂水平，我们从内分泌学临床注册中心收集体重指数(BMI)和APOA5突变亚型,并对10例重度HTG和APOA5基因变异患者进行回顾性队列研究.
结果：在10例中，四个是女性，六个是男性。中位年龄为45.0岁（最小-最大：21-60岁），甘油三酯（TG）中位数为2429.5mg/dL（27.5mmol/L）（min-max：1351-4087mg/dL，15.3-46.2mmol/L），平均BMI为30.4±4.4kg/m2（min-max：24.9-41.0kg/m2）。4例患有糖尿病（DM）；2例接受胰岛素强化治疗，还有两人在基础胰岛素治疗。平均血红蛋白A1c（HbA1c）为9.2±1.2％（min-max：8.3-11.0％）。在研究小组中，检测到8种不同的APOA5基因突变。这些变体在2例患者中是杂合的,在8例患者中是纯合的(双等位基因)。一名患者为APOA5p.Ser19Trp纯合，一种相对常见的多态性，是HTG的风险变异。
结论：我们报告了一组具有双等位基因和单拷贝APOA5变异的患者，在以后的生活中被诊断出来。大多数有次要因素，如DM，或BMI增加的肥胖。在我们的患者中发现的最罕见的APOA5变体具有不确定的意义。我们的研究结果增加了越来越多的证据，表明某些候选基因中的罕见变异可能容易发展成HTG，以及肥胖等次要因素。许多其他患者中HTG的遗传基础仍然未知，仍然是进一步研究的主题。
方法：人口统计，血脂水平，我们从内分泌学临床注册中心收集体重指数(BMI)和APOA5突变亚型,并对10例重度HTG和APOA5基因变异患者进行回顾性队列研究.
结果：在10例中，四个是女性，六个是男性。中位年龄为45.0岁（最小-最大：21-60岁），甘油三酯（TG）中位数为2429.5mg/dL（27.5mmol/L）（min-max：1351-4087mg/dL，15.3-46.2mmol/L），平均BMI为30.4±4.4kg/m2（min-max：24.9-41.0kg/m2）。4例患有糖尿病（DM）；2例接受胰岛素强化治疗，还有两人在基础胰岛素治疗。平均血红蛋白A1c（HbA1c）为9.2±1.2％（min-max：8.3-11.0％）。在研究小组中，检测到8种不同的APOA5基因突变。这些变体在2例患者中是杂合的,在8例患者中是纯合的(双等位基因)。一名患者为APOA5p.Ser19Trp纯合，一种相对常见的多态性，是HTG的风险变异。
结论：我们报告了一组具有双等位基因和单拷贝APOA5变异的患者，在以后的生活中被诊断出来。大多数有次要因素，如DM，或BMI增加的肥胖。在我们的患者中发现的最罕见的APOA5变体具有不确定的意义。我们的研究结果增加了越来越多的证据，表明某些候选基因中的罕见变异可能容易发展成HTG，以及肥胖等次要因素。许多其他患者中HTG的遗传基础仍然未知，仍然是进一步研究的主题。
