A Splice Region Variant in Lowers Non-high Density Lipoprotein Cholesterol and Protects against Coronary Artery Disease

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Cholesterol levels in the bloodstream, in particular elevated low-density lipoprotein cholesterol (LDL-C), are strong risk factors for cardiovascular disease, and LDL-C reduction reduces mortality in people at risk. One of the major determinants of plasma LDL-C levels is the low density lipoprotein receptor (LDLR) that acts as a scavenger for cholesterol rich lipoprotein particles. Mutations that disrupt the function of the LDLR or lead to reduction in the number of LDLR usually result in elevated LDL-C in blood. In the current study, we identified, through whole-genome sequencing and imputation into a large fraction of the Icelandic population, four LDLR gene variants that affect non-HDL-C levels (that includes cholesterol in LDL and other pro-atherogenic lipoproteins) and risk of coronary artery disease (CAD). Two variants are known and two are novel. One of them, a splice region variant in intron 14 (rs72658867-A), affects normal splicing and is predicted to generate a truncated LDLR, lacking domains essential for receptor function. Despite this, rs72658867-A lowers non-HDL-C substantially and protects against CAD in the general population, demonstrating that variants that disrupt the LDLR can result in lower cholesterol levels.

Vyšlo v časopise: A Splice Region Variant in Lowers Non-high Density Lipoprotein Cholesterol and Protects against Coronary Artery Disease. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005379
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005379

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