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(c) Elsevier Inc., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/174459

High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study

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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 (CARDloGRAMplusC4D, n = 184,305). We validated these results by defining our genetic variables in another database (METSINI, n = 8372) and studied their relationship with CAD in the CARDloGRAMplusC4D 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 (beta = 027 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (beta = 0.29 (95%CI = 0.17; 0.40]), and triglyceride content in very large HDIs (beta = 0.14 [95%CI = 0.040; 025]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (beta = -0.076 [95%CI = -0.10; -0.052]) was inversely related to this risk. These results were validated in the METSIM-CARDloGRAMplu5C4D 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. (C) 2020 Elsevier Inc. All rights reserved.

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PRATS URIBE, Albert, SAYOLS BAIXERAS, Sergi, FERNÁNDEZ SANLES, Alba, SUBIRANA, Isaac, CARRERAS TORRES, Robert, VILAHUR, Gemma, CIVEIRA, Fernando, MARRUGAT, Jaume, FITÓ COLOMER, Montserrat, HERNÁEZ CAMBA, Álvaro, ELOSUA, Roberto. High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study. _Metabolism Clinical and Experimental_. 2020. Vol. 112. [consulta: 25 de febrer de 2026]. [Disponible a: https://hdl.handle.net/2445/174459]

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