TY - JOUR
T1 - Ethnic diversity and distinctive features of familial versus multifactorial chylomicronemia syndrome: insights from the UK FCS National Registry
AU - Bashir, Bilal
AU - Downie, Paul
AU - Forrester, Natalie
AU - Wierzbicki, Anthony S.
AU - Dawson, Charlotte
AU - Jones, Alan
AU - Jenkinson, Fiona
AU - Mansfield, Michael
AU - Datta, Dev
AU - Delaney, Hannah
AU - Teoh, Yee
AU - Hamilton, Paul
AU - Ferdousi, Maryam
AU - Kwok, See
AU - O'Sullivan, Dawn
AU - Wang, Jian
AU - Hegele, Robert A.
AU - Durrington, Paul N.
AU - Soran, Handrean
PY - 2024/9/5
Y1 - 2024/9/5
N2 - 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.
AB - 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.
KW - body mass index
KW - cardiovascular diseases
KW - chylomicrons
KW - LDL
KW - lipoproteins
KW - pancreatitis
U2 - 10.1161/ATVBAHA.124.320955
DO - 10.1161/ATVBAHA.124.320955
M3 - Article
AN - SCOPUS:85203248154
SN - 1079-5642
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
ER -
