TY - JOUR
TI - Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
AU - Futema, M.
AU - Ramaswami, U.
AU - Tichy, L.
AU - Bogsrud, M.P.
AU - Holven, K.B.
AU - Roeters van Lennep, J.
AU - Wiegman, A.
AU - Descamps, O.S.
AU - De Leener, A.
AU - Fastre, E.
AU - Vrablik, M.
AU - Freiberger, T.
AU - Esterbauer, H.
AU - Dieplinger, H.
AU - Greber-Platzer, S.
AU - Medeiros, A.M.
AU - Bourbon, M.
AU - Mollaki, V.
AU - Drogari, E.
AU - Humphries, S.E.
JO - Atherosclerosis
PY - 2021
VL - 319
TODO - null
SP - 108-117
PB - Elsevier Ireland Ltd
SN - 0021-9150
TODO - 10.1016/j.atherosclerosis.2021.01.008
TODO - apolipoprotein B;  ezetimibe;  hydroxymethylglutaryl coenzyme A reductase inhibitor;  low density lipoprotein cholesterol;  low density lipoprotein receptor;  proprotein convertase 9;  lipid;  low density lipoprotein receptor;  PCSK9 protein, human;  proprotein convertase 9, Article;  Austria;  Belgium;  child;  comparative study;  controlled study;  Czech Republic;  familial hypercholesterolemia;  family history;  female;  gene mutation;  genetic susceptibility;  genotype phenotype correlation;  Greece;  heterozygosity;  human;  ischemic heart disease;  major clinical study;  male;  Netherlands;  Norway;  pediatric patient;  Portugal;  prematurity;  preschool child;  prevalence;  priority journal;  school child;  treatment outcome;  United Kingdom;  dna mutational analysis;  Europe;  familial hypercholesterolemia;  genetics;  mutation, Austria;  Belgium;  Child;  Czech Republic;  DNA Mutational Analysis;  Europe;  Greece;  Humans;  Hyperlipoproteinemia Type II;  Lipids;  Mutation;  Netherlands;  Norway;  Portugal;  Proprotein Convertase 9;  Receptors, LDL
TODO - Background and aims: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. Methods: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. Results: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10−16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10−16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). Conclusions: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH. © 2021 Elsevier B.V.
ER -