ArticleCirculation2008
Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment.
Article in Circulation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02488057 (Improving Beta Cell Function in Mexican American Women With Prediabetes), which is not on this map. Cited by 67 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Improving Beta Cell Function in Mexican American Women With Prediabetes
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.Arteriosclerosis, thrombosis, and vascular biology · 2008Pooled it
- Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy.PloS one · 2012Trial
- Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin.Arteriosclerosis, thrombosis, and vascular biology · 2010 · on this mapTrial
- Trial
- Genome-wide association of lipid-lowering response to statins in combined study populations.PloS one · 2010Trial
- Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol reduction and dose response.Circulation. Cardiovascular genetics · 2008 · on this mapTrial
- Ancestry gaps in cardiovascular GWAS: a multi-database review of African representation in genomic studies.Frontiers in genetics · 2025Review
- Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine.Scientific reports · 2024Article
- HMGCR gene polymorphism is associated with residual cholesterol risk in premature triple-vessel disease patients treated with moderate-intensity statins.BMC cardiovascular disorders · 2023Article
- Statistical methods for cis-Mendelian randomization with two-sample summary-level data.Genetic epidemiology · 2023Review
- Frequencies of variants in genes associated with dyslipidemias identified in Costa Rican genomes.Frontiers in genetics · 2023Article
- Personalized medicine in cardiovascular disease: review of literature.Journal of diabetes and metabolic disorders · 2021Review
- A Possible Role for HMG-CoA Reductase Inhibitors and Its Association withInternational journal of molecular sciences · 2021Review
- Associations between SNPs in Intestinal Cholesterol Absorption and Endogenous Cholesterol Synthesis Genes with Cholesterol Metabolism.Biomedicines · 2021Article
- 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
- Observational
- Genome-wide and Phenome-wide Approaches to Understand Variable Drug Actions in Electronic Health Records.Clinical and translational science · 2018Review
- Pharmacogenetics of Vascular Risk Factors in Alzheimer's Disease.Journal of personalized medicine · 2018Review
- Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner.The pharmacogenomics journal · 2017Article
7 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
16 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundUse of 3-hydroxyl-3-methylglutaryl-3 coenzyme A reductase (HMGCR) inhibitors, or statins, reduces cardiovascular disease risk by lowering plasma low-density lipoprotein cholesterol (LDL-C) concentrations. However, LDL-C response is variable and influenced by many factors, including racial ancestry, with attenuated response in blacks compared with whites. We hypothesized that single nucleotide polymorphisms in the gene encoding HMGCR, a rate-limiting enzyme in cholesterol synthesis and the direct enzymatic target of statins, contribute to variation in statin response. METHODS AND
resultsGenomic resequencing of HMGCR in 24 blacks and 23 whites identified 79 single nucleotide polymorphisms. Eleven single nucleotide polymorphisms were selected to tag common linkage disequilibrium clusters. These single nucleotide polymorphisms and the common haplotypes inferred from them were tested for association with plasma LDL-C and LDL-C response to simvastatin treatment (40 mg/d for 6 weeks) in 326 blacks and 596 whites. Black carriers of H7 and/or H2 had significantly lower baseline LDL-C (P=0.0006) and significantly attenuated LDL-C response compared with black participants who did not carry either haplotype as measured by absolute response (-1.23+/-0.04 mmol/L, n=209, versus -1.45+/-0.06 mmol/L, n=117; P=0.0008) and percent response (-36.9+/-1.0% versus -40.6+/-1.3%; P=0.02), but no haplotype effect was observed in whites. Percent LDL-C response was lowest in carriers of both H2 and H7, all but one of whom were black (-28.2+/-4.9%, n=12 H2+H7 carriers, versus -41.5+/-0.5%, n=650 H2/H7 noncarriers; P=0.001). LDL-C responses in H7 and/or H2 noncarriers were indistinguishable between blacks and whites.
conclusionsHMGCR gene polymorphisms are associated with reduced plasma LDL-C and LDL-C response to simvastatin, and these effects are most evident in blacks.
Indexed as
Identifiers
What Socratic 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 Socratic graph.