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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F21%3AN0000009" target="_blank" >RIV/00209775:_____/21:N0000009 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/21:10427343 RIV/65269705:_____/21:00074219 RIV/00064165:_____/21:10427343 RIV/00216224:14110/21:00121357

Result on the web

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0021915021000083" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0021915021000083</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.atherosclerosis.2021.01.008" target="_blank" >10.1016/j.atherosclerosis.2021.01.008</a>

Result language

angličtina

Original language name

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

Original language 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 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

<a href="/en/project/NU20-02-00261" target="_blank" >NU20-02-00261: Mechanisms of the effect of genetic variants of LDL receptor and the role of genetic variants of lipoprotein(a) in the development of hypercholesterolemia in FH patients</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Atherosclerosis

ISSN

0021-9150

e-ISSN

—

Volume of the periodical

319

Issue of the periodical within the volume

February 2021

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

10

Pages from-to

108-117

UT code for WoS article

000617764400004

EID of the result in the Scopus database

2-s2.0-85099858601