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

J 2021

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

FUTEMA, M., U. RAMASWAMI, Lukas TICHY, M. P. BOGSRUD, K. B. HOLVEN et. al.

Basic information

Original 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

Authors

FUTEMA, M., U. RAMASWAMI, Lukas TICHY (203 Czech Republic), M. P. BOGSRUD, K. B. HOLVEN, J. R. VAN LENNEP, A. WIEGMAN, OS DESCAMPS, A. DE LEENER, E. FASTRE, Michal VRABLIK (203 Czech Republic), Tomáš FREIBERGER (203 Czech Republic, belonging to the institution), H. ESTERBAUER, H. DIEPLINGER, S. GREBER-PLATZER, A. M. MEDEIROS, M. BOURBON, V. MOLLAKI, E. DROGARI and S. E. HUMPHRIES (guarantor)

Edition

Atherosclerosis, Clare, ELSEVIER SCI IRELAND LTD, 2021, 0021-9150

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.847

RIV identification code

RIV/00216224:14110/21:00121357

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.atherosclerosis.2021.01.008

UT WoS

000617764400004

Keywords in English

Heterozygous familial hypercholesterolaemia; Mutation spectrum; LDL-C concentrations; Statin treatment

Abstract

V originále

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.

Citovat

FUTEMA, M., U. RAMASWAMI, Lukas TICHY, M. P. BOGSRUD, K. B. HOLVEN, J. R. VAN LENNEP, A. WIEGMAN, OS DESCAMPS, A. DE LEENER, E. FASTRE, Michal VRABLIK, Tomáš FREIBERGER, H. ESTERBAUER, H. DIEPLINGER, S. GREBER-PLATZER, A. M. MEDEIROS, M. BOURBON, V. MOLLAKI, E. DROGARI and S. E. HUMPHRIES. 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. Atherosclerosis. Clare: ELSEVIER SCI IRELAND LTD, 2021, vol. 319, FEB 2021, p. 108-117. ISSN 0021-9150. Available from: https://dx.doi.org/10.1016/j.atherosclerosis.2021.01.008.

@article{1758051,
   author = {Futema, M. and Ramaswami, U. and Tichy, Lukas and Bogsrud, M. P. and Holven, K. B. and van Lennep, J. R. and Wiegman, A. and Descamps, OS and De Leener, A. and Fastre, E. and Vrablik, Michal and Freiberger, Tomáš and Esterbauer, H. and Dieplinger, H. and GreberandPlatzer, S. and Medeiros, A. M. and Bourbon, M. and Mollaki, V. and Drogari, E. and Humphries, S. E.},
   article_location = {Clare},
   article_number = {FEB 2021},
   doi = {http://dx.doi.org/10.1016/j.atherosclerosis.2021.01.008},
   keywords = {Heterozygous familial hypercholesterolaemia; Mutation spectrum; LDL-C concentrations; Statin treatment},
   language = {eng},
   issn = {0021-9150},
   journal = {Atherosclerosis},
   title = {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},
   url = {https://www.sciencedirect.com/science/article/pii/S0021915021000083?via%3Dihub},
   volume = {319},
   year = {2021}
}

TY  - JOUR
ID  - 1758051
AU  - 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.
PY  - 2021
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
JF  - Atherosclerosis
VL  - 319
IS  - FEB 2021
SP  - 108-117
EP  - 108-117
PB  - ELSEVIER SCI IRELAND LTD
SN  - 00219150
KW  - Heterozygous familial hypercholesterolaemia
KW  - Mutation spectrum
KW  - LDL-C concentrations
KW  - Statin treatment
UR  - https://www.sciencedirect.com/science/article/pii/S0021915021000083?via%3Dihub
N2  - 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.
ER  -

FUTEMA, M., U. RAMASWAMI, Lukas TICHY, M. P. BOGSRUD, K. B. HOLVEN, J. R. VAN LENNEP, A. WIEGMAN, OS DESCAMPS, A. DE LEENER, E. FASTRE, Michal VRABLIK, Tomáš FREIBERGER, H. ESTERBAUER, H. DIEPLINGER, S. GREBER-PLATZER, A. M. MEDEIROS, M. BOURBON, V. MOLLAKI, E. DROGARI and S. E. HUMPHRIES. 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. \textit{Atherosclerosis}. Clare: ELSEVIER SCI IRELAND LTD, 2021, vol.~319, FEB 2021, p.~108-117. ISSN~0021-9150. Available from: https://dx.doi.org/10.1016/j.atherosclerosis.2021.01.008.

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