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

Détails

Ressource 1Télécharger: 29567679_BIB_185181BE7AE3.pdf (684.86 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_185181BE7AE3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns.
Périodique
Arteriosclerosis, thrombosis, and vascular biology
Auteur(s)
Erhart G., Lamina C., Lehtimäki T., Marques-Vidal P., Kähönen M., Vollenweider P., Raitakari O.T., Waeber G., Thorand B., Strauch K., Gieger C., Meitinger T., Peters A., Kronenberg F., Coassin S.
ISSN
1524-4636 (Electronic)
ISSN-L
1079-5642
Statut éditorial
Publié
Date de publication
05/2018
Peer-reviewed
Oui
Volume
38
Numéro
5
Pages
1230-1241
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
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.
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.
Mots-clé
Adult, Aged, Apolipoproteins E/genetics, European Continental Ancestry Group/genetics, Female, Finland/epidemiology, Gene Frequency, Genetics, Population, Haplotypes, Humans, Lipoprotein(a)/blood, Lipoprotein(a)/genetics, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proprotein Convertase 9/genetics, Protein Isoforms, Risk Factors, atherosclerosis, genetics, population, lipoprotein(a), risk factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/03/2018 20:41
Dernière modification de la notice
30/04/2021 7:08
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