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Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns

OBJECTIVE—: Lp(a) (lipoprotein(a)) concentrations are widely genetically determined by the LPA isoforms and show 5-fold interpopulation differences. Two- to 3-fold differences have been reported even within Europe. Finns represent a distinctive population isolate within Europe and have been repeated...

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Autores principales: Erhart, Gertraud, Lamina, Claudia, Lehtimäki, Terho, Marques-Vidal, Pedro, Kähönen, Mika, Vollenweider, Peter, Raitakari, Olli T., Waeber, Gérard, Thorand, Barbara, Strauch, Konstantin, Gieger, Christian, Meitinger, Thomas, Peters, Annette, Kronenberg, Florian, Coassin, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943067/
https://www.ncbi.nlm.nih.gov/pubmed/29567679
http://dx.doi.org/10.1161/ATVBAHA.118.310865
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author Erhart, Gertraud
Lamina, Claudia
Lehtimäki, Terho
Marques-Vidal, Pedro
Kähönen, Mika
Vollenweider, Peter
Raitakari, Olli T.
Waeber, Gérard
Thorand, Barbara
Strauch, Konstantin
Gieger, Christian
Meitinger, Thomas
Peters, Annette
Kronenberg, Florian
Coassin, Stefan
author_facet Erhart, Gertraud
Lamina, Claudia
Lehtimäki, Terho
Marques-Vidal, Pedro
Kähönen, Mika
Vollenweider, Peter
Raitakari, Olli T.
Waeber, Gérard
Thorand, Barbara
Strauch, Konstantin
Gieger, Christian
Meitinger, Thomas
Peters, Annette
Kronenberg, Florian
Coassin, Stefan
author_sort Erhart, Gertraud
collection PubMed
description OBJECTIVE—: Lp(a) (lipoprotein(a)) concentrations are widely genetically determined by the LPA isoforms and show 5-fold interpopulation differences. Two- to 3-fold differences have been reported even within Europe. Finns represent a distinctive population isolate within Europe and have been repeatedly reported to present lower Lp(a) concentrations than Central Europeans. The significance of this finding was unclear for a long time because of the difficult comparability of Lp(a) assays. Recently, a large standardized study in >50 000 individuals from 7 European populations confirmed this observation but could not provide insights into the causes. APPROACH AND RESULTS—: We investigated Lp(a) concentrations, LPA isoforms, and genotypes of established genetic variants affecting Lp(a) concentrations (LPA variants, APOE isoforms, and PCSK9 R46L) in the Finnish YFS (Cardiovascular Risk in Young Finns Study) population (n=2281) and 3 Non-Finnish Central European populations (n=10 003). We observed ≈50% lower Lp(a) concentrations in Finns. The isoform distribution was shifted toward longer isoforms, and the percentage of low-molecular-weight isoform carriers was reduced. Most interestingly, however, Lp(a) was reduced in each single-isoform group. In contrast to the known inverse relationship between LPA isoforms and Lp(a) concentrations, especially very short isoforms presented unexpectedly low Lp(a) concentrations in Finns. The investigated genetic variants, as well as age, sex, and renal function, explained 71.8% of the observed population differences. CONCLUSIONS—: The population differences in Lp(a) concentrations between Finnish and Central European populations originate not only from a different LPA isoform distribution but suggest the existence of novel functional variation in the small-isoform range.
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spelling pubmed-59430672018-05-21 Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns Erhart, Gertraud Lamina, Claudia Lehtimäki, Terho Marques-Vidal, Pedro Kähönen, Mika Vollenweider, Peter Raitakari, Olli T. Waeber, Gérard Thorand, Barbara Strauch, Konstantin Gieger, Christian Meitinger, Thomas Peters, Annette Kronenberg, Florian Coassin, Stefan Arterioscler Thromb Vasc Biol Clinical and Population Studies OBJECTIVE—: Lp(a) (lipoprotein(a)) concentrations are widely genetically determined by the LPA isoforms and show 5-fold interpopulation differences. Two- to 3-fold differences have been reported even within Europe. Finns represent a distinctive population isolate within Europe and have been repeatedly reported to present lower Lp(a) concentrations than Central Europeans. The significance of this finding was unclear for a long time because of the difficult comparability of Lp(a) assays. Recently, a large standardized study in >50 000 individuals from 7 European populations confirmed this observation but could not provide insights into the causes. APPROACH AND RESULTS—: We investigated Lp(a) concentrations, LPA isoforms, and genotypes of established genetic variants affecting Lp(a) concentrations (LPA variants, APOE isoforms, and PCSK9 R46L) in the Finnish YFS (Cardiovascular Risk in Young Finns Study) population (n=2281) and 3 Non-Finnish Central European populations (n=10 003). We observed ≈50% lower Lp(a) concentrations in Finns. The isoform distribution was shifted toward longer isoforms, and the percentage of low-molecular-weight isoform carriers was reduced. Most interestingly, however, Lp(a) was reduced in each single-isoform group. In contrast to the known inverse relationship between LPA isoforms and Lp(a) concentrations, especially very short isoforms presented unexpectedly low Lp(a) concentrations in Finns. The investigated genetic variants, as well as age, sex, and renal function, explained 71.8% of the observed population differences. CONCLUSIONS—: The population differences in Lp(a) concentrations between Finnish and Central European populations originate not only from a different LPA isoform distribution but suggest the existence of novel functional variation in the small-isoform range. Lippincott Williams & Wilkins 2018-05 2018-03-22 /pmc/articles/PMC5943067/ /pubmed/29567679 http://dx.doi.org/10.1161/ATVBAHA.118.310865 Text en © 2018 The Authors. Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
spellingShingle Clinical and Population Studies
Erhart, Gertraud
Lamina, Claudia
Lehtimäki, Terho
Marques-Vidal, Pedro
Kähönen, Mika
Vollenweider, Peter
Raitakari, Olli T.
Waeber, Gérard
Thorand, Barbara
Strauch, Konstantin
Gieger, Christian
Meitinger, Thomas
Peters, Annette
Kronenberg, Florian
Coassin, Stefan
Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns
title Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns
title_full Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns
title_fullStr Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns
title_full_unstemmed Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns
title_short Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns
title_sort genetic factors explain a major fraction of the 50% lower lipoprotein(a) concentrations in finns
topic Clinical and Population Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943067/
https://www.ncbi.nlm.nih.gov/pubmed/29567679
http://dx.doi.org/10.1161/ATVBAHA.118.310865
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