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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
M. Futema, U. Ramaswami, L. Tichy, MP. Bogsrud, KB. Holven, J. Roeters van Lennep, A. Wiegman, OS. Descamps, A. De Leener, E. Fastre, M. Vrablik, T. Freiberger, H. Esterbauer, H. Dieplinger, S. Greber-Platzer, AM. Medeiros, M. Bourbon, V....
Language English Country Ireland
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
British Heart Foundation - United Kingdom
- MeSH
- Child MeSH
- Hyperlipoproteinemia Type II * diagnosis epidemiology genetics MeSH
- Receptors, LDL genetics MeSH
- Humans MeSH
- Lipids MeSH
- Mutation MeSH
- DNA Mutational Analysis MeSH
- Proprotein Convertase 9 * genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Belgium MeSH
- Czech Republic MeSH
- Europe MeSH
- Netherlands MeSH
- Norway MeSH
- Portugal MeSH
- Austria MeSH
- Greece MeSH
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.
1st Department of Pediatrics National and Kapodistrian University of Athens Greece
Centre de Génétique Humaine UCL Cliniques Universitaires Saint Luc Bruxelles Belgium
Centre of Molecular Biology and Gene Therapy University Hospital Brno Brno Czech Republic
Centres Hospitaliers Jolimont Lipid Clinic Haine Saint Paul Belgium
Department of Laboratory Medicine Medical University of Vienna Vienna Austria
Department of Nutrition University of Oslo Oslo Norway
Department of Pediatrics Amsterdam University Medical Centers Amsterdam the Netherlands
Departments of Cardiology and Internal Medicine Erasmus Medical Center Rotterdam the Netherlands
Lysosomal Disorders Unit Royal Free Hospital London United Kingdom
References provided by Crossref.org
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- $a Futema, Marta $u Centre for Heart Muscle Disease, Institute for Cardiovascular Science, University College London, London, United Kingdom
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- $a 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 / $c M. Futema, U. Ramaswami, L. Tichy, MP. Bogsrud, KB. Holven, J. Roeters van Lennep, A. Wiegman, OS. Descamps, A. De Leener, E. Fastre, M. Vrablik, T. Freiberger, H. Esterbauer, H. Dieplinger, S. Greber-Platzer, AM. Medeiros, M. Bourbon, V. Mollaki, E. Drogari, SE. Humphries
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- $a 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.
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