ArticleProceedings of the National Academy of Sciences of the United States of America2004
Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- Renal sympathetic nerve activation via αKidney research and clinical practice · 2019Article
- The association of an alpha2C adrenoreceptor gene polymorphism with vasomotor symptoms in African American women.Menopause (New York, N.Y.) · 2019Article
- Genetic variation in alpha2-adrenoreceptors and heart rate recovery after exercise.Physiological genomics · 2015Article
- Common α2A and α2C adrenergic receptor polymorphisms do not affect plasma membrane trafficking.Naunyn-Schmiedeberg's archives of pharmacology · 2014Article
- Intracellular α(2C)-adrenoceptors: storage depot, stunted development or signaling domain?Biochimica et biophysica acta · 2011Review
- Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.Nature medicine · 2010Article
- Common ADRB2 haplotypes derived from 26 polymorphic sites direct beta2-adrenergic receptor expression and regulation phenotypes.PloS one · 2010Article
- Using patient DNA to optimize therapy in heart failure patients: a move toward perfection.Heart failure reviews · 2010Article
- Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells.British journal of pharmacology · 2010Article
- Effects of variation in the human alpha2A- and alpha2C-adrenoceptor genes on cognitive tasks and pain perception.European journal of pain (London, England) · 2010Article
- Pharmacogenomics of beta1-adrenergic receptor polymorphisms in heart failure.Heart failure clinics · 2010Review
- Mechanisms of pharmacogenomic effects of genetic variation within the cardiac adrenergic network in heart failure.Molecular pharmacology · 2009Review
- The alpha2C-adrenoceptor deletion322-325 variant and cold-induced vasoconstriction.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2009Article
- Multiple interactions between the alpha 2C- and beta1-adrenergic receptors influence heart failure survival.BMC medical genetics · 2008Article
- Variable-length poly-C tract polymorphisms of the beta2-adrenergic receptor 3'-UTR alter expression and agonist regulation.American journal of physiology. Lung cellular and molecular physiology · 2008Article
- Tight control of adrenal medulla catecholamine release by alpha 2C-adrenergic receptors influences susceptibility to heart failure.Cardiovascular research · 2007Article
- The Gordon Wilson Lecture: neurohormonal signaling pathways that link cardiac growth and death.Transactions of the American Clinical and Climatological Association · 2007Article
- Alpha-adrenoceptor gene variants and autonomic nervous system function in a young healthy Japanese population.Journal of human genetics · 2007Article
- Generalized genomic distance-based regression methodology for multilocus association analysis.American journal of human genetics · 2006Article
- Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The presynaptic alpha2C adrenergic receptors (AR) act to inhibit norepinephrine release in cardiac and other presynaptic nerves. We have recently shown that a genetic variant in the alpha2CAR coding region (Del322-325), which renders the receptor partially uncoupled from Gi, is a risk factor for heart failure. However, variability of heart failure phenotypes and a dominance of Del322-325 in those of African descent led us to hypothesize that other regions of this gene have functional polymorphisms. In a multiethnic population, we found 20 polymorphisms within 4,625 bp of contiguous sequence of this intronless gene encompassing the promoter, 5' UTR, coding, and 3' UTR. These polymorphisms occur in 24 distinct haplotypes with complex organizations, including multiple 5'-upstream polymorphisms in regions known to direct expression, a 3' UTR substitution polymorphism within an insertion/deletion sequence, and the radical coding polymorphism that deletes four amino acids. Relatively low linkage disequilibrium between many polymorphisms, few cosmopolitan haplotypes, prevalent ethnic-specific haplotypes, and substantial genetic divergence among haplotypes was noted. The dysfunctional Del322-325 allele was partitioned into multiple haplotypes, with frequencies of 48% to 2%. The functional implications of the haplotypes were ascertained by whole-gene transfections of human neuronal cells, where haplotype was significantly related (P < 0.001) to expression levels of receptor transcript and protein. Expression varied by as much as approximately 50% by haplotype, and such studies enabled haplotype clustering by phenotypic, rather than genotypic, similarities. Thus, depending on phenotype, expression-specific haplotypes may amplify, attenuate, or dominate the cardiomyopathic effect attributed to the alpha2CDel322-325 marker.
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