Genetic variation at the human alpha2B-adrenergic receptor locus: role in blood pressure variation and yohimbine response
| Autor: | Robert J. Parmer, Paul A. Insel, Jason P. Etzel, Daniel T. O'Connor, Gen Wen, Nicholas J. Schork, Brinda K. Rana |
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| Rok vydání: | 2005 |
| Předmět: |
Candidate gene
medicine.medical_specialty Genotype Black People Locus (genetics) Blood Pressure Biology Essential hypertension White People Cohort Studies Receptors Adrenergic alpha-2 Internal medicine Genetic variation Internal Medicine medicine Humans Genetic Predisposition to Disease Adrenergic alpha-Antagonists Genetics Polymorphism Genetic Haplotype Chromosome Mapping Genetic Variation Yohimbine Genomics medicine.disease Endocrinology Blood pressure Haplotypes Hypertension medicine.drug |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 45(6) |
| ISSN: | 1524-4563 |
| Popis: | Exaggerated response to α 2 -adrenergic receptor (α 2 -AR) blockade by yohimbine in normotensive subjects is an intermediate phenotype that predicts increased risk for development of hypertension. Here, we assessed the 3 α 2 -AR loci (α 2A, α 2B, α 2C ) as candidate genes for their influence on baseline and yohimbine-mediated increase in mean arterial pressure. Because initial results with 173 individuals implicated a possible association of yohimbine response with genetic variation at a site in the α 2B -AR gene, but not at sites in the other 2 α 2 -AR, we sequenced the α 2B -AR gene (4.4 kb, including 1.2 kb upstream and 1.9 kb distal to the coding sequence) in those subjects and an additional 81 individuals to search for other α 2B -AR variants. We identified 25 polymorphisms, of which 14 are previously unreported, and 2 major haplotypes that differ by the presence/absence of a 9-bp in-frame deletion that encodes Glu 301 to Glu 303 . Frequency differences in haplotypes were observed between blacks and whites but did not predict response to yohimbine. Genotyping of 2 additional white cohorts, including 1269 individuals with extremes in blood pressure selected from >50 000 subjects, also failed to reveal an association of the 2 major α 2B -AR haplotypes with differences in blood pressure. Thus, despite considerable polymorphism in α 2 -AR genes, such variation is not a major determinant of variability in yohimbine response and by inference, in susceptibility to essential hypertension. |
| Databáze: | OpenAIRE |
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