Genetic variation within adrenergic pathways determines in vivo effects of presynaptic stimulation in humans

Circulation
Maple M FungDaniel T O'Connor

Abstract

Catecholamines govern stress blood pressure responses. Catecholaminergic responses may be partially genetic and contribute to the complex heritability of hypertension. To evaluate catecholaminergic responses without systemic counterregulation, we infused graded concentrations of tyramine, an indirect presynaptic norepinephrine releaser, into dorsal hand veins of 49 normotensive men and women of 5 ethnicities. Vascular responses were coupled to common (minor allele frequency >10%) single-nucleotide polymorphisms at adrenergic target loci within presynaptic pathways. Significance was set at P<0.003 after Bonferroni correction. Generalized analysis of molecular variance (GAMOVA) was performed to determine whether genetic admixture contributed to results. Venoconstriction progressed to 47% with increasing concentrations of tyramine (0.129 to 25.8 mmol/L; P<0.001). Family history of hypertension (P<0.001) and female sex (P=0.02) predicted blunted tyramine responses. Two genetic loci significantly predicted vascular response: chromogranin B, which encodes a protein that catalyzes catecholamine vesicle formation (CHGB, exon 4, Glu348Glu; P=0.002), and cytochrome b-561 (CYB561, intron 1, C719G; P<0.001), an electron shuttle for catecho...Continue Reading

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Citations

Mar 11, 2010·Journal of Hypertension·Kuixing ZhangDaniel T O'Connor
Dec 17, 2010·Forensic Science International : Synergy·Stefano D'ErricoVittorio Fineschi
Nov 27, 2009·Forensic Science International : Synergy·Vittorio FineschiEmanuela Turillazzi
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Jan 30, 2008·Circulation·David S Goldstein
Jun 4, 2010·Circulation. Heart Failure·Helge RøsjøGeir Christensen

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