ArticleThe Journal of clinical investigation2011
The N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population.PloS one · 2015Trial
- Transcriptomic Analysis in the Liver of Two Rabbit Lines Divergently Selected for Intramuscular Fat Content.Animal genetics · 2026Article
- Review
- Is IDOL an Ideal Target for Treating Atherosclerosis?Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Influence of the IDOL Gene Variants on Low-Density Lipoprotein Cholesterol Levels in Turkish Patients with Familial Hypercholesterolemia.Molecular syndromology · 2025Article
- A Comprehensive Review of the Genetics of Dyslipidemias and Risk of Atherosclerotic Cardiovascular Disease.Nutrients · 2025Review
- Development of a novel Guinea Pig model producing transgenerational endothelial transcriptional changes driven by maternal food restriction and a second metabolic insult of high fat diet.Frontiers in physiology · 2023Article
- Rare Variants in Genes of the Cholesterol Pathway Are Present in 60% of Patients with Acute Myocardial Infarction.International journal of molecular sciences · 2022Article
- Pharmacogenomics of statins: lipid response and other outcomes in Brazilian cohorts.Pharmacological reports : PR · 2022Review
- Idol Depletion Protects against Spontaneous Atherosclerosis in a Hamster Model of Familial Hypercholesterolemia.Oxidative medicine and cellular longevity · 2022Article
- IDOL regulates systemic energy balance through control of neuronal VLDLR expression.Nature metabolism · 2019Article
- Genomic Basis of Convergent Island Phenotypes in Boa Constrictors.Genome biology and evolution · 2019Article
- The complex molecular genetics of familial hypercholesterolaemia.Nature reviews. Cardiology · 2019Review
- Inactivation of the E3 Ubiquitin Ligase IDOL Attenuates Diet-Induced Obesity and Metabolic Dysfunction in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Liver X receptors in lipid signalling and membrane homeostasis.Nature reviews. Endocrinology · 2018Review
- miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules.Oncotarget · 2017Article
- Genetic determinants of inherited susceptibility to hypercholesterolemia - a comprehensive literature review.Lipids in health and disease · 2017Review
- A powerful statistical framework for generalization testing in GWAS, with application to the HCHS/SOL.Genetic epidemiology · 2017Article
- Stable liver-specific expression of human IDOL in humanized mice raises plasma cholesterol.Cardiovascular research · 2016Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Atherosclerotic cardiovascular disease (ASCVD) affects more than 1 in 3 American adults. Hypercholesterolemia is a major treatable risk factor for ASCVD, yet many individuals fail to reach target levels of LDL-cholesterol (LDL-C) through the use of statins and lifestyle changes. The E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP; also known as IDOL) is a recently identified regulator of the LDL receptor (LDLR) pathway. Genome-wide association studies (GWASs) in populations of mixed European descent have identified noncoding variants in the MYLIP region as being associated with LDL-C levels, but no underlying functional variants were pinpointed. In order to fine-map actual susceptibility variants, we studied a population demographically distinct from the discovery population to ensure a different pattern of linkage disequilibrium. Our analysis revealed that in a Mexican population, the nonsynonymous SNP rs9370867, which encodes the N342S amino acid substitution, is an underlying functional variant that was associated with high total cholesterol and accounted for one of the previous significant GWAS signals. Functional characterization showed that the Asn-encoding allele was associated with more potent LDLR degradation and decreased LDL uptake. Mutagenesis of residue 342 failed to affect intrinsic MYLIP E3 ligase activity, but it was critical for LDLR targeting. Our findings suggest that modulation of MYLIP activity can affect LDL-C levels and that pharmacologic inhibition of MYLIP activity might be a useful strategy in the treatment of dyslipidemia and ASCVD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.