A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

Détails

Ressource 1Télécharger: J. Lipid Res.-2017-Mack-1834-44.pdf (1262.30 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_5A3A28A604C2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.
Périodique
Journal of lipid research
Auteur(s)
Mack S., Coassin S., Rueedi R., Yousri N.A., Seppälä I., Gieger C., Schönherr S., Forer L., Erhart G., Marques-Vidal P., Ried J.S., Waeber G., Bergmann S., Dähnhardt D., Stöckl A., Raitakari O.T., Kähönen M., Peters A., Meitinger T., Strauch K., Kedenko L., Paulweber B., Lehtimäki T., Hunt S.C., Vollenweider P., Lamina C., Kronenberg F.
Collaborateur(s)
KORA-Study Group
ISSN
1539-7262 (Electronic)
ISSN-L
0022-2275
Statut éditorial
Publié
Date de publication
09/2017
Peer-reviewed
Oui
Volume
58
Numéro
9
Pages
1834-1844
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis
Publication Status: ppublish
Résumé
High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the <i>LPA</i> and 1 SNP in the <i>APOE</i> gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the <i>LPA</i> , 1 in the <i>APOE</i> gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio = 1.73, <i>P</i> = 3.35 × 10 <sup>-30</sup> ). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the <i>APOE2</i> -determining allele of rs7412 to be significantly associated with Lp(a) concentrations ( <i>P</i> = 3.47 × 10 <sup>-10</sup> ). Each <i>APOE2</i> allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the population's mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the <i>TLR2</i> gene with Lp(a) ( <i>P</i> = 3.4 × 10 <sup>-4</sup> ). In summary, we identified a large number of independent SNPs in the <i>LPA</i> gene region, as well as the <i>APOE2</i> allele, to be significantly associated with Lp(a) concentrations.

Mots-clé
Animals, Apolipoproteins A/genetics, Apolipoproteins A/metabolism, Genome-Wide Association Study/methods, Humans, Lipoprotein(a)/genetics, Lipoprotein(a)/metabolism, Polymorphism, Single Nucleotide, Protein Isoforms/metabolism, Sex Characteristics, coronary artery disease, epidemiology, genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/05/2017 17:14
Dernière modification de la notice
08/05/2019 19:02
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