SynthesisArteriosclerosis, thrombosis, and vascular biology2008
Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.
Synthesis in Arteriosclerosis, thrombosis, and vascular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Twenty-Five Novel Loci for Carotid Intima-Media Thickness: A Genome-Wide Association Study in >45 000 Individuals and Meta-Analysis of >100 000 Individuals.Arteriosclerosis, thrombosis, and vascular biology · 2022Pooled it
- Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study.PLoS genetics · 2011Pooled it
- Impact of mRNA and protein isoforms in lipoprotein metabolism and how to modulate them.Current opinion in lipidology · 2026Review
- A six-year longitudinal study identifies a statin-independent association between low LDL-cholesterol and risk of type 2 diabetes.Cardiovascular diabetology · 2025Article
- Alternative Splicing Regulation in Metabolic Disorders.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Genome-wide association study for circulating metabolic traits in 619,372 individuals.medRxiv : the preprint server for health sciences · 2025Article
- Genetic Polymorphisms in theInternational journal of molecular sciences · 2024Article
- Integration of multidimensional splicing data and GWAS summary statistics for risk gene discovery.PLoS genetics · 2022Article
- LPL, FNDC5 and PPARγ gene polymorphisms related to body composition parameters and lipid metabolic profile in adolescents from Southern Italy.Journal of translational medicine · 2022Article
- Associations between SNPs in Intestinal Cholesterol Absorption and Endogenous Cholesterol Synthesis Genes with Cholesterol Metabolism.Biomedicines · 2021Article
- A compendium of uniformly processed human gene expression and splicing quantitative trait loci.Nature genetics · 2021Article
- A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial HypercholesterolemiaIranian biomedical journal · 2021Article
- Identifying genetic modulators of statin response using subject-derived lymphoblastoid cell lines.Pharmacogenomics · 2021Review
- Genome-wide association studies in Samoans give insight into the genetic architecture of fasting serum lipid levels.Journal of human genetics · 2021Article
- Personalised medicine in hypercholesterolaemia: the role of pharmacogenetics in statin therapy.Annals of medicine · 2020Review
- Association study of rs3846662 with Alzheimer's disease in a population-based cohort: the Cache County Study.Neurobiology of aging · 2019Article
- Genetic effects on promoter usage are highly context-specific and contribute to complex traits.eLife · 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
- Genome-wide and Phenome-wide Approaches to Understand Variable Drug Actions in Electronic Health Records.Clinical and translational science · 2018Review
10 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
14 authors at 5 institutions in 1 country.
Funding
Abstract
unlabelledBackground- Variation in LDL-cholesterol (LDL-C) among individuals is a complex genetic trait involving multiple genes and gene-environment interactions. METHODS AND
resultsIn a genome-wide association study (GWAS) to identify genetic variants influencing LDL-C in an isolated population from Kosrae, we observed associations for SNPs in the gene encoding 3hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR). Three of these SNPs (rs7703051, rs12654264, and rs3846663) met the statistical threshold of genome-wide significance when combined with data from the Diabetes Genetics Initiative GWAS. We followed up the association results and identified a functional SNP in intron13 (rs3846662), which was in linkage disequilibrium with the SNPs of genome-wide significance and affected alternative splicing of HMGCR mRNA. In vitro studies in human lymphoblastoid cells demonstrated that homozygosity for the rs3846662 minor allele was associated with up to 2.2-fold lower expression of alternatively spliced HMGCR mRNA lacking exon13, and minigene transfection assays confirmed that allele status at rs3846662 directly modulated alternative splicing of HMGCR exon13 (42.9+/-3.9 versus 63.7+/-1.0%Deltaexon13/total HMGCR mRNA, P=0.02). Further, the alternative splice variant could not restore HMGCR activity when expressed in HMGCR deficient UT-2 cells.
conclusionsWe identified variants in HMGCR that are associated with LDL-C across populations and affect alternative splicing of HMGCR exon13.
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What OpenQuestion holds
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.