| beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. | |
| | |
MedLine Citation:
|
PMID: 16815314 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVES: The human beta(1)-adrenergic receptor, an important therapeutic target in cardiovascular diseases, has 2 common functional polymorphisms (Ser49Gly and Gly389Arg). Our study aimed to confirm that beta(1)-adrenergic receptor polymorphisms affect the blood pressure response to metoprolol monotherapy in the Chinese population with hypertension. METHODS: beta(1)-Adrenergic receptor genotype was determined by polymerase chain reaction-restriction fragment length polymorphism assay for 223 patients with essential hypertension. Sixty-one patients with certain beta(1)-adrenergic receptor diplotypes, 18 for 49Ser389Arg/49Ser389Arg, 15 for 49Ser389Arg/49Gly389Arg, 19 for 49Ser389Gly/49Gly389Arg, and 9 for 49Ser389Gly/49Ser389Gly, were selected from those 61 for measurement of the antihypertensive effect of metoprolol. Patients were given 25 mg metoprolol every 12 hours for 4 weeks. Heart rate and blood pressure were measured weekly for the duration of metoprolol therapy. RESULTS: The descent of systolic blood pressure after metoprolol administration was significantly different among genotype groups (10.4% +/- 4.0%, 2.8% +/- 4.7%, and 1.1% +/- 1.5% for Arg389Arg, Gly389Arg, and Gly389Gly patients, respectively; P < .001). We also found a similar difference in changes of diastolic blood pressure (6.1% +/- 4.3%, 2.2% +/- 4.2%, and 0.9% +/- 4.0%, respectively; P < .001) and mean arterial pressure (8.1% +/- 3.5%, 2.5% +/- 3.0%, and 1.0% +/- 2.5%, respectively; P > .001) for Arg389Arg, Gly389Arg, and Gly389Gly patients. Ser49Gly variance exhibited a smaller contribution to the antihypertensive effect of metoprolol. Systolic blood pressure decreased significantly in Ser49 homozygous patients compared with Ser49Gly patients (8.4% +/- 3.2% versus 5.3% +/- 5.2%, P = .047). There was a highly significant relationship between diplotype and blood pressure during treatment. Systolic blood pressure significantly decreased in 49Ser389Arg/49Ser389Arg (12.0% +/- 3.8%, P < .001) and 49Ser389Arg/49Gly389Arg (8.4% +/- 5.5%, P < .001) patients, with the decrease in the former being more pronounced (P = .023). We also found a significant decrease in diastolic blood pressure (6.5% +/- 4.7% versus 5.7% +/- 3.2%, respectively; both P < .001) and mean arterial pressure (8.8% +/- 3.2% versus 6.9% +/- 3.7%, respectively; both P < .001) in 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients. However, blood pressure did not change significantly in 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients (all P > .05). CONCLUSIONS: beta(1)-Adrenergic receptor polymorphism was associated with different blood pressure responses to metoprolol therapy in patients with essential hypertension. 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients were good responders to metoprolol therapy; 49Ser389Arg/49Ser389Arg patients had a larger systolic blood pressure reduction than 49Ser389Arg/49Gly389Arg patients did. 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients were nonresponders to metoprolol antihypertensive therapy. |
| | |
Authors:
|
Jie Liu; Zhao-Qian Liu; Bang-Ning Yu; Fang-Hua Xu; Wei Mo; Gan Zhou; Ying-Zi Liu; Qing Li; Hong-Hao Zhou |
Related Documents
:
|
7387254 - Central antihypertensive activity of propranolol. 6142004 - Efficacy and tolerance of the new long-acting vasodilator ro 12-4713 in hypertensive pa... 3525084 - Indoramin. a review of its pharmacodynamic and pharmacokinetic properties, and therapeu... 2425174 - Cardiac and lymphocyte beta-adrenoceptors in perinephritis hypertension in the rabbit. 12780984 - High-frequency oscillation in children after fontan operation. 10215714 - Theatre monitor alarm settings: a pilot survey in scotland and belgium. |
Publication Detail:
|
Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't Date: 2006-06-08 |
Journal Detail:
|
Title: Clinical pharmacology and therapeutics Volume: 80 ISSN: 0009-9236 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2006 Jul |
Date Detail:
|
Created Date: 2006-07-03 Completed Date: 2006-08-03 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 23-32 Citation Subset: AIM; IM |
Affiliation:
|
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenergic beta-Antagonists
/
therapeutic use* Blood Pressure / drug effects China Female Humans Hypertension / drug therapy* Male Metoprolol / therapeutic use* Middle Aged Pharmacogenetics Polymorphism, Genetic Polymorphism, Restriction Fragment Length Receptors, Adrenergic, beta / genetics* |
| Chemical | |
Reg. No./Substance:
|
0/Adrenergic beta-Antagonists; 0/Receptors, Adrenergic, beta; 37350-58-6/Metoprolol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genot...
Next Document: Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study.