ArticleCirculation2008
Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin.
Article in Circulation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Genetic variants modulate gene expression statin response in human lymphoblastoid cell lines.BMC genomics · 2020Pooled it
- ZNF542P is a pseudogene associated with LDL response to simvastatin treatment.Scientific reports · 2018Trial
- Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels.PloS one · 2013Trial
- Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin.Arteriosclerosis, thrombosis, and vascular biology · 2010 · on this mapTrial
- Pharmacogenomics of Atherosclerotic Plaque: Pathophysiological Background and Therapeutic Perspectives.Current atherosclerosis reports · 2026Review
- Impact of mRNA and protein isoforms in lipoprotein metabolism and how to modulate them.Current opinion in lipidology · 2026Review
- Characterizing the genetic architecture of drug response using gene-context interaction methods.Cell genomics · 2024Article
- Genetic Polymorphisms in theInternational journal of molecular sciences · 2024Article
- Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response.Genome medicine · 2024Article
- Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine.Scientific reports · 2024Article
- Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk.Genes · 2023Review
- HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.BMC cardiovascular disorders · 2023Article
- RNA-seq reveals insights into molecular mechanisms of metabolic restoration via tryptophan supplementation in low birth weight piglet model.Journal of animal science · 2022Article
- A Possible Role for HMG-CoA Reductase Inhibitors and Its Association withInternational journal of molecular sciences · 2021Review
- Review
- Extending the lymphoblastoid cell line model for drug combination pharmacogenomics.Pharmacogenomics · 2021Review
- Identifying genetic modulators of statin response using subject-derived lymphoblastoid cell lines.Pharmacogenomics · 2021Review
- Association study of rs3846662 with Alzheimer's disease in a population-based cohort: the Cache County Study.Neurobiology of aging · 2019Article
- Therapeutic targets of hypercholesterolemia: HMGCR and LDLR.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Influence of 6 genetic variants on the efficacy of statins in patients with dyslipidemia.Journal of clinical laboratory analysis · 2018Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHMGCR(3-Hydroxy-3-methylglutaryl coenzyme A reductase), the direct target of statin inhibition, undergoes alternative splicing of exon 13, which encodes part of the statin-binding domain of the enzyme. We hypothesized that HMGCR alternative splicing might be related to the interindividual variation in plasma low-density lipoprotein cholesterol response to statin treatment. METHODS AND
resultsWe measured mRNA expression of both the full-length and the alternatively spliced HMGCR transcript lacking exon 13 (HMGCRv_1) in 170 simvastatin-incubated immortalized lymphocyte cell lines derived from participants in the Cholesterol and Pharmacogenetics (CAP) study who were treated with simvastatin 40 mg/d for 6 weeks. Greater upregulation of HMGCRv_1 in vitro was significantly correlated (P<or=0.0001) with smaller in vivo reductions of plasma total cholesterol, low-density lipoprotein cholesterol, apoprotein B, and triglycerides and explained 6% to 15% of the variation in their response to treatment. In contrast, no significant relationship was found between expression of the full-length HMGCR transcript and in vivo response. By siRNA knockdown of the full-length transcript, we found that HMGCR enzyme activity measured in cells enriched in HMGCRv_1 was relatively resistant to statin inhibition, consistent with the association of increased alternative splicing with reduced statin response in the CAP study. In addition, we found that a common HMGCR single-nucleotide polymorphism (rs3846662) located within intron 13 was associated with variation in the proportion of HMGCR mRNA that is alternatively spliced.
conclusionsVariation in the production of an HMGCR isoform with reduced statin sensitivity is a determinant of interindividual differences in low-density lipoprotein cholesterol, apolipoprotein B, and triglyceride response to statin treatment.
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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.