High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
Autor/a
Fitó Colomer, Montserrat
Hernáez, Álvaro
Elosua Llanos, Roberto
Otros/as autores/as
Universitat Ramon Llull. Facultat de Ciències de la Salut Blanquerna
Fecha de publicación
2020-09Resumen
Background
To assess whether genetically determined quantitative and qualitative HDL characteristics were independently associated with coronary artery disease (CAD).
Methods
We designed a two-sample multivariate Mendelian randomization study with available genome-wide association summary data. We identified genetic variants associated with HDL cholesterol and apolipoprotein A-I levels, HDL size, particle levels, and lipid content to define our genetic instrumental variables in one sample (Kettunen et al. study, n = 24,925) and analyzed their association with CAD risk in a different study (CARDIoGRAMplusC4D, n = 184,305). We validated these results by defining our genetic variables in another database (METSIM, n = 8372) and studied their relationship with CAD in the CARDIoGRAMplusC4D dataset. To estimate the effect size of the associations of interest adjusted for other lipoprotein traits and minimize potential pleiotropy, we used the Multi-trait-based Conditional & Joint analysis.
Results
Genetically determined HDL cholesterol and apolipoprotein A-I levels were not associated with CAD. HDL mean diameter (β = 0.27 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (β = 0.29 [95%CI = 0.17; 0.40]), and triglyceride content in very large HDLs (β = 0.14 [95%CI = 0.040; 0.25]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (β = −0.076 [95%CI = -0.10; −0.052]) was inversely related to this risk. These results were validated in the METSIM-CARDIoGRAMplusC4D data.
Conclusions
Some qualitative HDL characteristics (related to size, particle distribution, and cholesterol and triglyceride content) are related to CAD risk while HDL cholesterol levels are not.
Tipo de documento
Artículo
Versión del documento
Versión aceptada
Lengua
English
Materias (CDU)
616.1 - Patología del sistema circulatorio, de los vasos sanguíneos. Transtornos cardiovasculares
Palabras clave
Lipoproteïnes de densitat alta
Sistema cardiovascular -- Malalties
Variables aleatòries
Aleatorització Mendeliana
Malalties coronàries
Páginas
7 p.
Publicado por
Elsevier
Publicado en
Metabolism Clinical and Experimental, 2020, 112: 154351
Número del acuerdo de la subvención
info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/CD17/00122
info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/IFI14/00007
info:eu-repo/grantAgreement/MINECO/ISCIII i FEDER/PI18/00017
info:eu-repo/grantAgreement/MRC/MR/K501256/1
info:eu-repo/grantAgreement/MRC/MR/N013468/1
info:eu-repo/grantAgreement/MINECO/PN I+D/BES-2014-069718
info:eu-repo/grantAgreement/MINECO/PN I+D/SAF2015-71653-R
info:eu-repo/grantAgreement/EU/H2020/796216
info:eu-repo/grantAgreement/SUR del DEC/SGR/2017 SGR 222
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Derechos
© Elsevier. Tots els drets reservats