Faculty of Biology Medicine and Health, University of Manchester, United Kingdom (B.B., M.F., P.N.D., H.S.).
Department of Endocrinology, Diabetes and Metabolism, Manchester University NHS Foundation Trust, United Kingdom (B.B., S.K., H.S.).
Arterioscler Thromb Vasc Biol. 2024 Nov;44(11):2334-2346. doi: 10.1161/ATVBAHA.124.320955. Epub 2024 Sep 5.
Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder. This study aimed to study the genotype distribution of FCS-causing genes in the United Kingdom, genotype-phenotype correlation, and clinical differences between FCS and multifactorial chylomicronemia syndrome (MCS).
The study included 154 patients (FCS, 74; MCS, 80) from the UK FCS national registry and the UK arm of the FCS International Quality Improvement and Service Evaluation Project.
FCS was relatively common in non-Europeans and those with parental consanguinity (<0.001 for both). variants were more common in European patients with FCS (European, 64%; non-European, 46%), while the genotype was more diverse in non-European patients with FCS. Patients with FCS had a higher incidence compared with patients with MCS of acute pancreatitis (84% versus 60%; =0.001), recurrent pancreatitis (92% versus 63%; <0.001), unexplained abdominal pain (84% versus 52%; <0.001), earlier age of onset (median [interquartile range]) of symptoms (15.0 [5.5-26.5] versus 34.0 [25.2-41.7] years; <0.001), and of acute pancreatitis (24.0 [10.7-31.0] versus 33.5 [26.0-42.5] years; <0.001). Adverse cardiometabolic features and their co-occurrence was more common in individuals with MCS compared with those with FCS (<0.001 for each). Atherosclerotic cardiovascular disease was more prevalent in individuals with MCS than those with FCS (=0.04). However, this association became nonsignificant after adjusting for age, sex, and body mass index. The prevalence of pancreatic complications and cardiometabolic profile of variant-positive MCS was intermediate between FCS and variant-negative MCS.
The frequency of gene variant distribution varies based on the ethnic origin of patients with FCS. Patients with FCS are at a higher risk of pancreatic complications while the prevalence of atherosclerotic cardiovascular disease is lower in FCS compared with MCS. Carriers of heterozygous pathogenic variants have an intermediate phenotype between FCS and variant-negative MCS.
家族性乳糜微粒血症综合征（FCS）是一种罕见的常染色体隐性遗传疾病。本研究旨在研究英国 FCS 致病基因的基因型分布、基因型-表型相关性以及 FCS 与多因素乳糜微粒血症综合征（MCS）之间的临床差异。
该研究纳入了来自英国 FCS 国家注册中心和 FCS 国际质量改进和服务评估项目英国分部的 154 名患者（FCS 患者 74 名，MCS 患者 80 名）。
FCS 在非欧洲裔人群和有父母近亲结婚者中较为常见（均<0.001）。欧洲 FCS 患者携带 FCS 变异的频率更高（欧洲患者，64%；非欧洲患者，46%），而非欧洲 FCS 患者的基因型则更为多样化。与 MCS 患者相比，FCS 患者发生急性胰腺炎的比例更高（84%比 60%；=0.001）、复发性胰腺炎的比例更高（92%比 63%；<0.001）、不明原因腹痛的比例更高（84%比 52%；<0.001）、症状发病年龄更早（中位数[四分位距]）（15.0[5.5-26.5]比 34.0[25.2-41.7]岁；<0.001）、急性胰腺炎发病年龄更早（24.0[10.7-31.0]比 33.5[26.0-42.5]岁；<0.001）。与 FCS 患者相比，MCS 患者更常出现不良的心血管代谢特征及其共同发生（每项均<0.001）。与 FCS 患者相比，MCS 患者发生动脉粥样硬化性心血管疾病的比例更高（=0.04）。然而，在调整年龄、性别和体重指数后，这种关联不再具有统计学意义。携带杂合致病性变异的患者的表型位于 FCS 和变异阴性 MCS 之间。
FCS 患者的基因变异分布频率因种族来源而异。与 MCS 相比，FCS 患者发生胰腺并发症的风险更高，而动脉粥样硬化性心血管疾病的发生率则较低。杂合致病性变异携带者的表型位于 FCS 和变异阴性 MCS 之间。
