Document Detail


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
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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.
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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


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