Publication details

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

Authors	FUTEMA M. RAMASWAMI U. TICHY Lukas BOGSRUD M. P. HOLVEN K. B. VAN LENNEP J. R. WIEGMAN A. DESCAMPS OS DE LEENER A. FASTRE E. VRABLIK Michal FREIBERGER Tomáš ESTERBAUER H. DIEPLINGER H. GREBER-PLATZER S. MEDEIROS A. M. BOURBON M. MOLLAKI V. DROGARI E. HUMPHRIES S. E.
Year of publication	2021
Type	Article in Periodical
Magazine / Source	Atherosclerosis
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://www.sciencedirect.com/science/article/pii/S0021915021000083?via%3Dihub
Doi	http://dx.doi.org/10.1016/j.atherosclerosis.2021.01.008
Keywords	Heterozygous familial hypercholesterolaemia; Mutation spectrum; LDL-C concentrations; Statin treatment
Description	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 preand 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 x 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 x 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.