Common gene variants in ASGR1 gene locus associate with reduced cardiovascular risk in absence of pleiotropic effects.

Atherosclerosis
Lubna AliMarjolein A W van den Boogert

Abstract

The rare ASGR1 del12 variant is associated with a beneficial effect on coronary artery disease (CAD) that is disproportionate to the small reductions in plasma LDL cholesterol (LDLc). This unexplained benefit has sparked the debate on potential additional pleiotropic effects of ASGR1 variants. Since ASGR1 has also been implicated in platelet homeostasis, we evaluated platelet function in heterozygous ASGR1 del12 carriers and controls. In addition, we compared the magnitude of various LDLc lowering genetic scores in the UK-biobank using Mendelian randomization. Desialylation of platelet surface glycoproteins and platelet aggregation capacity were measured in 12 carriers and 10 controls. We selected 3 common genetic variants in the ASGR1 locus that were significantly associated with plasma LDLc and assessed the association with coronary artery disease (CAD) and compared it with the effects of HMCGR, LDLR, NCI1L1 and PCSK9 gene scores. Platelet surface GlcNAC residues were significantly lower in carriers but platelet aggregation did not differ. The relative risk reduction of ASGR1 GRS on CAD and myocardial infarction per 10 mg/dl LDLc reduction was 23% (OR 0.77, 95% CI 0.62-0.96). This risk reduction was proportionally similar to ...Continue Reading

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Citations

Sep 5, 2020·Cardiovascular Research·Angela PirilloGiuseppe Danilo Norata
May 8, 2021·Atherosclerosis·Christoph J BinderArnold von Eckardstein
Oct 5, 2021·Current Opinion in Hematology·Leonardo RivadeneyraKarin M Hoffmeister

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