Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/45218
Title: Genetic Susceptibility Loci for Cardiovascular Disease and Their Impact on Atherosclerotic Plaques.
Authors: van der Laan, SW
Siemelink, MA
Haitjema, S
Foroughi Asl, H
Perisic, L
Mokry, M
van Setten, J
Malik, R
Dichgans, M
Worrall, BB
METASTROKE Collaboration of the International Stroke Genetics Consortium
Samani, NJ
Schunkert, H
Erdmann, J
Hedin, U
Paulsson-Berne, G
Björkegrenn, JLM
de Borst, GJ
Asselbergs, FW
den Ruijter, FW
de Bakker, PIW
Pasterkamp, G
First Published: 17-Sep-2018
Publisher: American Heart Association, Lippincott, Williams & Wilkins
Citation: Circulation: Genomic and Precision Medicine, 2018, 11:e002115
Abstract: BACKGROUND: Atherosclerosis is a chronic inflammatory disease in part caused by lipid uptake in the vascular wall, but the exact underlying mechanisms leading to acute myocardial infarction and stroke remain poorly understood. Large consortia identified genetic susceptibility loci that associate with large artery ischemic stroke and coronary artery disease. However, deciphering their underlying mechanisms are challenging. Histological studies identified destabilizing characteristics in human atherosclerotic plaques that associate with clinical outcome. To what extent established susceptibility loci for large artery ischemic stroke and coronary artery disease relate to plaque characteristics is thus far unknown but may point to novel mechanisms. METHODS: We studied the associations of 61 established cardiovascular risk loci with 7 histological plaque characteristics assessed in 1443 carotid plaque specimens from the Athero-Express Biobank Study. We also assessed if the genotyped cardiovascular risk loci impact the tissue-specific gene expression in 2 independent biobanks, Biobank of Karolinska Endarterectomy and Stockholm Atherosclerosis Gene Expression. RESULTS: A total of 21 established risk variants (out of 61) nominally associated to a plaque characteristic. One variant (rs12539895, risk allele A) at 7q22 associated to a reduction of intraplaque fat, P=5.09×10-6 after correction for multiple testing. We further characterized this 7q22 Locus and show tissue-specific effects of rs12539895 on HBP1 expression in plaques and COG5 expression in whole blood and provide data from public resources showing an association with decreased LDL (low-density lipoprotein) and increase HDL (high-density lipoprotein) in the blood. CONCLUSIONS: Our study supports the view that cardiovascular susceptibility loci may exert their effect by influencing the atherosclerotic plaque characteristics.
DOI Link: 10.1161/CIRCGEN.118.002115
eISSN: 2574-8300
Links: https://www.ahajournals.org/doi/10.1161/CIRCGEN.118.002115
http://hdl.handle.net/2381/45218
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Description: The Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCGEN.118.002115
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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