ArticleBritish journal of clinical pharmacology2009
A common NOS1AP genetic polymorphism is associated with increased cardiovascular mortality in users of dihydropyridine calcium channel blockers.
Article in British journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Pooled it
- Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.Clinical and translational science · 2026Article
- Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.Pharmacogenomics and personalized medicine · 2024Article
- Antihypertensives associated adverse events: a review of mechanisms and pharmacogenomic biomarkers available evidence in multi-ethnic populations.Frontiers in pharmacology · 2023Review
- Article
- Genetics and genomics of arrhythmic risk: current and future strategies to prevent sudden cardiac death.Nature reviews. Cardiology · 2021Review
- NOS1AP polymorphisms reduce NOS1 activity and interact with prolonged repolarization in arrhythmogenesis.Cardiovascular research · 2021Article
- Article
- NOS1AP modulates intracellular Ca(2+) in cardiac myocytes and is up-regulated in dystrophic cardiomyopathy.International journal of physiology, pathophysiology and pharmacology · 2014Article
- Nitric Oxide Synthase 1 Adaptor Protein, an Emerging New Genetic Marker for QT Prolongation and Sudden Cardiac Death.Acta Cardiologica Sinica · 2013Review
- Cardiovascular pharmacogenomics: the future of cardiovascular therapeutics?The Canadian journal of cardiology · 2013Review
- Cardiovascular pharmacogenomics.Circulation research · 2011Review
- Pharmacogenomics: the genetics of variable drug responses.Circulation · 2011Review
- Drug-induced long QT syndrome.Pharmacological reviews · 2010Review
- Sudden cardiac death prediction and prevention: report from a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop.Circulation · 2010Article
- NOS1AP is a genetic modifier of the long-QT syndrome.Circulation · 2009Article
- S-Nitrosylation of cardiac ion channels.Journal of cardiovascular pharmacology · 2009Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimRecently, a polymorphism in the NOS1AP gene (rs10494366), a regulator of neuronal nitric oxide synthase (nNOS), was associated with QTc prolongation. Both nNOS and calcium channel blockers (CCBs) regulate intracellular calcium levels and have an important role in cardiovascular homeostasis. The aim was to investigate whether this polymorphism is associated with cardiovascular mortality in users of CCBs.
methodsThe data from the Rotterdam study, a population-based closed cohort study of Caucasian individuals of > or =55 years of age, were used. We identified 1113 participants in the Rotterdam Study who were prescribed CCBs for the first time between 1991 and 2005. All-cause and cardiovascular mortality was assessed in participants who were prescribed CCBs with different NOS1AP rs10494366 genotypes using Cox proportional hazard models.
resultsIn participants starting on dihydropyridine CCBs (amlodipine, nifedipine and others) all-cause mortality (n = 79) risks were higher in participants with the TG [hazard ratio (HR) 2.57, 95% confidence interval (CI) 1.24, 5.34] or the GG genotype (HR 3.18, 95% CI 1.18, 8.58) than in participants with the referent TT genotype. Cardiovascular mortality (n = 54) risks were 3.51 (95% CI 1.41, 8.78) for the TG genotype and 6.00 (95% CI 1.80, 20.0) for the GG genotype. No differences in all-cause mortality or cardiovascular mortality were seen in participants starting with the nondihydropyridine CCBs verapamil or diltiazem.
conclusionThe minor G allele of rs10494366 in the NOS1AP gene is associated with increased all-cause and cardiovascular mortality in Caucasian users of dihydropyridine CCBs. The mechanism underlying the observed association is unknown.
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