Document Detail


Polymorphic variants of the beta2-adrenergic receptor (ADRB2) gene and ADRB2-related propanolol-induced dyslipidemia in the Colombian population.
MedLine Citation:
PMID:  16082424     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Different polymorphisms of the ADRB2 gene encoding the beta-adrenergic receptor (ADRB2) are associated with changes in a variety of responses of the sympathetic nervous system (SNS). In this study, we have investigated the distribution of frequencies of ADRB2-related allelic variants (Arg16Gly, Gln27Glu, Thr164Ile) in the Colombian population, as well as the influence of the Gln27Glu polymorphism as a risk factor for the development of dyslipidemia following propranolol administration. Genotyping was performed in unrelated Colombian volunteers, using PCR-RFLP methods. To examine the association between the Gln27Glu polymorphism of the ADRB2 gene and dyslipidemia induced by propranolol, we recruited 19 healthy individuals who were homozygous for either the Gln27 (wild-type, N = 11) or the Glu27 (homozygous mutant, N = 8) genotype. Electrocardiography (ECG), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum lipid levels (T-CHO, HDL-CHO, TG), and fibrinogen were determined before and after propranolol administration. The distribution of genotypes was as follows: Arg16Arg 46%, Arg16Gly 47.4%, Gly16Gly 6.6%, Gln27Gln 44.7%, Gln27Glu 48.2%, and Glu27Glu 7.1%, with allelic frequencies of 69.7% for Arg16, 30.3% for Gly16, 68.8% for Gln27, and 31.2% for Glu27. The Thr164Ile polymorphism was found only in one subject, who was heterozygous for the isoleucine variant. Significant changes in physiological parameters (HR, SBP, DBP) have been found in association with ADRB2 variants in both native and mutant subgroups after propranolol intake. HDL-CHO levels diminished (p = 0.005) in native homozygous individuals (Gln27Gln), whereas TG levels were found increased (p = 0.012) in the mutant homozygous individuals (Glu27Glu). T-CHO levels and serum fibrinogen levels remained unaltered in both subgroups. The evidence that subjects homozygous for Gln27 in the ADRB2 gene show a significant reduction of HDL-CHO levels, as well as the increased TG levels in subjects homozygous for Glu27 after propranolol administration, suggest that the Gln27Glu polymorphism represents a risk factor for dyslipidemia induced by propranolol. These results may contribute to a better understanding of the mechanisms underlying dyslipidemia induced by ADRB2 antagonists.
Authors:
C Isaza; J Henao; E Ramirez; F Cuesta; R Cacabelos
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Methods and findings in experimental and clinical pharmacology     Volume:  27     ISSN:  0379-0355     ISO Abbreviation:  Methods Find Exp Clin Pharmacol     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-08-05     Completed Date:  2005-09-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7909595     Medline TA:  Methods Find Exp Clin Pharmacol     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  237-44     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Prous Science. All rights reserved.
Affiliation:
Laboratory of Medical Genetics, Pereira Technological University Medical School, Pereira, Colombia.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adrenergic beta-Antagonists / blood,  pharmacology*
Adult
Blood Pressure / drug effects
Cholesterol, HDL / drug effects,  metabolism
Colombia / epidemiology
Female
Gene Frequency
Genotype
Heart Rate / drug effects
Humans
Hyperlipidemias / chemically induced,  genetics*,  physiopathology
Male
Phenotype
Polymorphism, Genetic
Propranolol / blood,  pharmacology*
Receptors, Adrenergic, beta-2 / genetics*
Triglycerides / metabolism
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Cholesterol, HDL; 0/Receptors, Adrenergic, beta-2; 0/Triglycerides; 525-66-6/Propranolol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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