ArticleCirculation. Cardiovascular genetics2009
CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response.
Article in Circulation. Cardiovascular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00133692 (INternational VErapamil SR Trandolapril STudy), which is not on this map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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.
INternational VErapamil SR Trandolapril STudy
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome-Wide Interaction Meta-Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies.Clinical pharmacology and therapeutics · 2021Pooled it
- Trial
- Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes.The pharmacogenomics journal · 2018Trial
- CACNA1C polymorphisms Impact Cognitive Recovery in Patients with Bipolar Disorder in a Six-week Open-label Trial.Scientific reports · 2017Trial
- Association between CACNA1C gene polymorphisms and ritodrine-induced adverse events in preterm labor patients.European journal of clinical pharmacology · 2017Trial
- Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function.The Journal of clinical investigation · 2017Trial
- Pharmacogenomics-guided therapy for essential hypertension: a multi-center randomized controlled open-label trial.Frontiers in cardiovascular medicine · 2026Article
- mRNA Isoforms and Variants in Health and Disease.International journal of molecular sciences · 2025Review
- Pathophysiologic Mechanisms of Cardiovascular Disease in Patients With Bipolar Disorder.Cureus · 2025Review
- Article
- Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.Pharmacogenomics and personalized medicine · 2024Article
- No association between genetic markers and hypertension control in multiple cross-sectional studies.Scientific reports · 2023Article
- Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity.Medicina (Kaunas, Lithuania) · 2023Article
- Pharmacogenetic association of theFrontiers in pharmacology · 2023Article
- Management of Hypertension in the Elderly and Frail Patient.Drugs & aging · 2022Article
- Article
- Pharmacogenomics in Cardiovascular Diseases.Current protocols · 2021Article
- Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules.BMC endocrine disorders · 2021Article
- Variants inInternational journal of general medicine · 2021Article
- Pharmacogenomics of Hypertension Treatment.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe gene encoding the target of calcium channel blockers, the alpha1c-subunit of the L-type calcium channel (CACNA1C), has not been well characterized, and only small pharmacogenetic studies testing this gene have been published to date. METHODS AND
resultsResequencing of CACNA1C was performed followed by a nested case-control study of the INternational VErapamil SR/trandolapril STudy (INVEST) GENEtic Substudy (INVEST-GENES). Of 46 polymorphisms identified, 8 were assessed in the INVEST-GENES. Rs1051375 was found to have a significant interaction with treatment strategy (P=0.0001). Rs1051375 A/A genotype was associated with a 46% reduction in the primary outcome among those randomized to verapamil SR treatment, when compared with atenolol treatment (odds ratio 0.54 95% CI 0.32 to 0.92). In heterozygous A/G individuals, there was no difference in the occurrence of the primary outcome when randomized to verapamil SR versus atenolol treatment (odds ratio 1.47 95% CI 0.86 to 2.53), whereas homozygous G/G individuals had a greater than 4-fold increased risk of the primary outcome with verapamil treatment compared with those randomized to atenolol treatment (odds ratio 4.59 95% CI 1.67 to 12.67). We did not identify allelic expression imbalance or differences in mRNA expression in heart tissue by rs1051375 genotype.
conclusionsVariation in CACNA1C is associated with treatment response among hypertensive patients with stable coronary artery disease. Our data suggest a genetically defined group of patients that benefit most from calcium channel blocker therapy, a group that benefits most from beta-blocker therapy, and a third group in which calcium channel blocker and beta-blocker therapy are equivalent.
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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.