ArticleBMC medical genetics2008
Multiple interactions between the alpha 2C- and beta1-adrenergic receptors influence heart failure survival.
Article in BMC medical genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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.
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Who cites it
9 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Common α2A and α2C adrenergic receptor polymorphisms do not affect plasma membrane trafficking.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Pharmacogenomics and cardiovascular disease.Current cardiology reports · 2013Review
- The T allele of lysyl oxidase-like 1 rs41435250 is a novel risk factor for pseudoexfoliation syndrome and pseudoexfoliation glaucoma independently and through intragenic epistatic interaction.Molecular vision · 2013Article
- Genetic determinants of response to cardiovascular drugs.Current opinion in cardiology · 2012Review
- Association of in vivo β-adrenergic receptor sensitivity with inflammatory markers in healthy subjects.Psychosomatic medicine · 2012Article
- Cardiovascular pharmacogenomics of adrenergic receptor signaling: clinical implications and future directions.Clinical pharmacology and therapeutics · 2011Review
- Progress toward genetic tailoring of heart failure therapy.Current opinion in molecular therapeutics · 2010Review
- Molecular remodeling of ion channels, exchangers and pumps in atrial and ventricular myocytes in ischemic cardiomyopathy.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundPersistent stimulation of cardiac beta1-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the alpha 2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively) on the risk of death/transplant in heart failure patients.
methodsSixteen sequence variations in ADRA2C and 17 sequence variations in ADRB1 were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation.
resultsThree polymorphisms in ADRA2C and five polymorphisms in ADRB1 were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18) relative to all other genotype classes.
conclusionMultiple polymorphisms act synergistically between the ADRA2C and ADRB1 genes to increase risk of death or cardiac transplant in heart failure patients.
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