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Lookup NU author(s): Dr Fiona Jenkinson
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2024 The Authors.BACKGROUND: 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). METHODS: 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. RESULTS: FCS was relatively common in non-Europeans and those with parental consanguinity (P<0.001 for both). LPL 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%; P=0.001), recurrent pancreatitis (92% versus 63%; P<0.001), unexplained abdominal pain (84% versus 52%; P<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; P<0.001), and of acute pancreatitis (24.0 [10.7-31.0] versus 33.5 [26.0-42.5] years; P<0.001). Adverse cardiometabolic features and their co-occurrence was more common in individuals with MCS compared with those with FCS (P<0.001 for each). Atherosclerotic cardiovascular disease was more prevalent in individuals with MCS than those with FCS (P=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. CONCLUSIONS: 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.
Author(s): Bashir B, Downie P, Forrester N, Wierzbicki AS, Dawson C, Jones A, Jenkinson F, Mansfield M, Datta D, Delaney H, Teoh Y, Hamilton P, Ferdousi M, Kwok S, O'Sullivan D, Wang J, Hegele RA, Durrington PN, Soran H
Publication type: Article
Publication status: Published
Journal: Arteriosclerosis, Thrombosis, and Vascular Biology
Year: 2024
Pages: epub ahead of print
Online publication date: 05/09/2024
Acceptance date: 09/08/2024
Date deposited: 17/09/2024
ISSN (print): 1079-5642
ISSN (electronic): 1524-4636
Publisher: Lippincott Williams and Wilkins
URL: https://doi.org/10.1161/ATVBAHA.124.320955
DOI: 10.1161/ATVBAHA.124.320955
PubMed id: 39234690
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