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A common variant in CCDC93 protects against myocardial infarction and cardiovascular mortality by regulating endosomal trafficking of low-density lipoprotein receptor

Eur Heart J. 2020; 
Rimbert A, Dalila N, Wolters JC, Huijkman N, Smit M, Kloosterhuis N, Riemsma M, van der Veen Y, Singla A, van Dijk F; Biobank-Based Integrative Omics Studies Consortium, Frikke-Schmidt R, Burstein E, Tybj?rg-Hansen A, , van de Sluis B, Kuivenhoven JA.
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摘要

Genome-wide association studies have previously identified INSIG2 as a candidate gene for plasma low-density lipoprotein cholesterol (LDL-c). However, we suspect a role for CCDC93 in the same locus because of its involvement in the recycling of the LDL-receptor (LDLR).,Characterization of the INSIG2 locus was followed by studies in over 107?000 individuals from the general population, the Copenhagen General Population Study and the Copenhagen City Heart Study, for associations of genetic variants with plasma lipids levels, with risk of myocardial infarction (MI) and with cardiovascular mortality. CCDC93 was furthermore studied in cells and mice. The lead variant of the INSIG2 locus (rs10490626) is not associat... More

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