Genetic Variation of the Beta-2 Adrenergic Receptor and the Phenylethanolamine N-Methyltransferase Enzyme: Influence on Catecholamines, Cardiovascular Regulation, and the Cardiopulmonary Response to Albuterol

Persistent Link:
http://hdl.handle.net/10150/317802
Title:
Genetic Variation of the Beta-2 Adrenergic Receptor and the Phenylethanolamine N-Methyltransferase Enzyme: Influence on Catecholamines, Cardiovascular Regulation, and the Cardiopulmonary Response to Albuterol
Author:
Martinez, Marina G.
Issue Date:
2014
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Hypertension, or chronic blood pressure elevation, affects approximately a third of American adults and is responsible for $70 billion dollars annually in medical costs. Recent studies have attempted to identify genetic variants that influence cardiopulmonary function, including blood pressure regulation. This study seeks to determine whether a polymorphism in position -182 of the gene encoding the phenylethanolamine N-methyltransferase (PNMT) enzyme, which converts norepinephrine to epinephrine, influences catecholamine levels and cardiovascular function. Secondly, this study seeks to explore whether a polymorphism at amino acid position 16 of the beta-2 adrenergic receptor (B2AR) affects the cardiovascular response to albuterol in healthy individuals; this study also explores the pulmonary response to albuterol in healthy subjects and patients with cystic fibrosis according to B2AR genotype. All subjects were genotyped and stratified according to genotype. Baseline measurements were taken. Albuterol was administered via nebulizer. Cardiopulmonary measurements were taken again at 30-, 60-, and 90- minutes post-albuterol administration. This study found that the PNMT polymorphism at position -182 influences circulating epinephrine, the epinephrine:norepinephrine ratio, and cardiac output. The B2AR polymorphism at amino acid position 16 affects the percent change in systemic vascular resistance in response to albuterol administration in healthy subjects. Furthermore, this study found that the B2AR polymorphism at amino acid 16 affects the change in forced vital capacity following albuterol administration in cystic fibrosis subjects.
Type:
text; Electronic Dissertation
Keywords:
blood pressure; cardiovascular; genetic variation; pulmonary; Physiological Sciences; albuterol
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Snyder, Eric; Konhilas, John

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleGenetic Variation of the Beta-2 Adrenergic Receptor and the Phenylethanolamine N-Methyltransferase Enzyme: Influence on Catecholamines, Cardiovascular Regulation, and the Cardiopulmonary Response to Albuterolen_US
dc.creatorMartinez, Marina G.en_US
dc.contributor.authorMartinez, Marina G.en_US
dc.date.issued2014-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractHypertension, or chronic blood pressure elevation, affects approximately a third of American adults and is responsible for $70 billion dollars annually in medical costs. Recent studies have attempted to identify genetic variants that influence cardiopulmonary function, including blood pressure regulation. This study seeks to determine whether a polymorphism in position -182 of the gene encoding the phenylethanolamine N-methyltransferase (PNMT) enzyme, which converts norepinephrine to epinephrine, influences catecholamine levels and cardiovascular function. Secondly, this study seeks to explore whether a polymorphism at amino acid position 16 of the beta-2 adrenergic receptor (B2AR) affects the cardiovascular response to albuterol in healthy individuals; this study also explores the pulmonary response to albuterol in healthy subjects and patients with cystic fibrosis according to B2AR genotype. All subjects were genotyped and stratified according to genotype. Baseline measurements were taken. Albuterol was administered via nebulizer. Cardiopulmonary measurements were taken again at 30-, 60-, and 90- minutes post-albuterol administration. This study found that the PNMT polymorphism at position -182 influences circulating epinephrine, the epinephrine:norepinephrine ratio, and cardiac output. The B2AR polymorphism at amino acid position 16 affects the percent change in systemic vascular resistance in response to albuterol administration in healthy subjects. Furthermore, this study found that the B2AR polymorphism at amino acid 16 affects the change in forced vital capacity following albuterol administration in cystic fibrosis subjects.en_US
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectblood pressureen_US
dc.subjectcardiovascularen_US
dc.subjectgenetic variationen_US
dc.subjectpulmonaryen_US
dc.subjectPhysiological Sciencesen_US
dc.subjectalbuterolen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorSnyder, Ericen_US
dc.contributor.advisorKonhilas, Johnen_US
dc.contributor.committeememberSnyder, Ericen_US
dc.contributor.committeememberKonhilas, Johnen_US
dc.contributor.committeememberRegan, Johnen_US
dc.contributor.committeememberNix, Daviden_US
dc.contributor.committeememberCohen, Zoeen_US
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