Polymorphism in the b 1 Adrenergic Receptor Gene and Hypertension (original) (raw)
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Polymorphism in the β 1 -Adrenergic Receptor Gene and Hypertension
Circulation, 2001
Background — The Arg389 variant of the β 1 -adrenergic receptor gene mediates a higher isoproterenol-stimulated adenylate cyclase activity than the Gly389 variant in vitro. We investigated whether the Arg389Gly or the Ser49Gly polymorphism is associated with hypertension in Scandinavians. Methods and Results — A total of 292 unrelated, nondiabetic, hypertensive patients and 265 unrelated healthy control subjects were included in a case-control association study. From 118 families, 102 nondiabetic sibling pairs without antihypertensive medication who were discordant for the Arg389Gly polymorphism were selected for a sibling study. Allele and genotype frequencies of the Arg389Gly and Ser49Gly polymorphisms were compared between hypertensive patients and normotensive control subjects. Blood pressure and heart rate were compared between carriers of the different genotypes. In the case-control study, the age- and body mass index-adjusted odds ratio for hypertension in subjects homozygous...
Journal of Human Hypertension, 2005
The Arg16Gly and the Gln27Glu polymorphisms in the gene for the b 2-adrenergic receptor (b 2 AR) have been linked to an increased risk for cardiovascular disease. The aim of the present study was to evaluate the significance of these haplotypes for development of myocardial infarction (MI) as well as other cardiovascular phenotypes. In a prospective study cohort (CAPPP), 522 hypertensive patients (174 MI and 348 matched controls) were analysed for the Arg16Gly and the Gln27Glu polymorphisms by dynamic allele-specific hybridisation. The haplotype could successfully be determined in 516 patients. Haplotype was not significantly associated with MI. Systolic blood pressure (SBP) was higher in patients with Arg16Gly þ Gln27Gln and lower in patients with Arg16Gly þ Gln27Glu as compared with the other haplotypes. Haplotype was not associated with body mass index, diastolic blood pressure, cholesterol, LDL, HDL triglycerides or a diagnosis of diabetes mellitus. The present study found no evidence that haplotype for the two most common polymorphisms in the b 2 AR are associated with development of MI in a Swedish hypertensive population, but haplotype may be associated with SBP.
β-Adrenergic Receptor Gene Polymorphisms and β-Blocker Treatment Outcomes in Hypertension
Clinical Pharmacology & Therapeutics, 2008
Numerous studies have demonstrated that β 1-and β 2-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and β-blocker responses in hypertension and heart failure. We evaluated the relationship between ADRB1 and ADRB2 haplotypes, cardiovascular risk (death, nonfatal myocardial infarction (MI), and nonfatal stroke), and atenolol-based vs. verapamil sustained-release (SR)-based antihypertensive therapy in 5,895 coronary artery disease (CAD) patients. After an average of 2.8 years, death rates were higher in patients carrying the ADRB1 Ser49-Arg389 haplotype (hazard ratio (HR) 3.66, 95% confidence interval (95% CI) 1.68-7.99). This mortality risk was significant in patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06-35.8) but not atenolol (HR 2.31, 95% CI 0.82-6.55), suggesting a protective role for the β-blocker. ADRB2 haplotype associations were divergent within the treatment groups but did not remain significant after adjustment for multiple comparisons. ADRB1 haplotype variation is associated with mortality risk, and β-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2 polymorphisms. Cardiovascular disease is the leading cause of morbidity and mortality in the United States. 1 Evidence is accumulating that genetic polymorphisms may be predictive of cardiovascular risk. 2,3 Moreover, several studies have identified genetic factors that influence blood pressure and metabolic responses to β-blockers, thiazide diuretics, and renin-angiotensin system antagonists. 4 Whether such pharmacogenetic differences translate to differences in the clinical outcome of antihypertensive therapy is less clear, particularly when patients receive multiple drugs that are titrated to a target blood pressure. 5 A pharmacogenetic approach to treating hypertension could not only reduce the number and cost of medications but also reduce morbidity and mortality if the outcome of drug treatment differs by genotype.
Kidney International, 1998
-2 Adrenoceptor genetic variation is associated with genetic predisposition to essential hypertension: The Bergen Blood Pressure Study. We tested the hypothesis that genetic variation in the -2 adrenoceptor gene is associated with a genetic predisposition to hypertension. Offspring of two hypertensive parents were compared with offspring of two normotensive parents. The subjects were participants of the Bergen Blood Pressure Study, where couples were recruited in 1963 to 1964 and re-examined in 1990. We studied offspring of those couples in which both partners were either hypertensive or normotensive in both examinations. Twenty-three hypertensive and 22 normotensive families met the inclusion criteria. DNA samples from the first born of hypertensive family-history offspring and normotensive family-history offspring were analyzed. We used multiplex sequencing and specifically examined the promoter and the Nterminal portion of the -2 adrenoceptor gene. We found four genetic variants: at position Ϫ47, a C3 T substitution in the 5Ј leader cistron causing an Arg3 Cys exchange, at Ϫ20, a T3 C substitution, at ϩ46 an A3 G substitution leading to an Arg163 Gly exchange, and at ϩ79, a C3 G substitution leading to a Gln273 Glu exchange. The frequency of the Arg16 allele was significantly higher in the hypertensive family-history offspring compared to normotensive family-history offspring (58% vs. 28%, P Ͻ 0.011). We constructed haplotypes for the four intragenic variants and found significant linkage dysequilibrium. In particular, the 5Ј leader cistron mutant with the wild type alleles at the other loci was significantly more frequent in offspring of hypertensive parents, compared to offspring of normotensive parents. We also performed a relative risk analysis comparing the Gly/Gly, Arg/Gly, and Arg/Arg alleles, which implicated the Arg-containing allele. Finally, we analyzed the effect of genotype on blood pressure in the offspring. We found a signficant step-wise effect for all four polymorphisms examined. Our data suggest that the Arg variant of the Arg3 Gly exchange is associated with parental hypertension and higher blood pressure values in this northern European population.
American Journal of Hypertension, 2004
Several case-control studies have explored the possible association between polymorphism in the  2 adrenoreceptor gene ( 2 AR), hypertension, and obesitythe focus being in particular on the Arg16Gly and Gln27Glu substitutions, which appear to modify the extracellular part of the  2 AR with possible functional modification. However, controversial results have been obtained. Design and Methods: The analysis refers to 993 middle-age men characterized for Arg16Gly and Gln27Glu polymorphism of the  2 AR. In this general population sample there were 563 overweight, 160 obese, and 405 hypertensive individuals, of whom 171 were receiving antihypertensive therapy. Results: The genotype frequencies for codon 16 were: GlyGly ϭ 38%; ArGly ϭ 45%; ArgArg ϭ 17%. The frequencies for codon 27 were: GlnGln ϭ 50%; GlnGlu ϭ 39%; GluGlu ϭ 11%. Codon 16 and codon 27 polymorphisms were in linkage disequilibrium. No differences were detected in body mass index and blood pressure across different genotypes. Likewise, no association was detected between either of the two polymorphisms and being overweight (codon 27: 2 ϭ 0.1, codon 16: 2 ϭ 1.4), obesity (codon 27: 2 ϭ 0.1, codon 16: 2 ϭ 1.7) and hypertension (codon 27: 2 ϭ 2.7, codon 16: 2 ϭ 1.9). The odds ratio (with 95% confidence intervals) for overweight, obesity, and hypertension were not different between genotypes. Likewise, no difference in the anthropometric indices of fat distribution, fasting blood glucose, serum insulin, triglycerides, uric acid, and HOMA index could be detected between groups. Conclusions: In summary, in this large unselected sample of adult white men, genetic variation in the  2 AR was not associated with blood pressure or with overweight, obesity, and fat distribution.
The Medical journal of Malaysia, 2012
Polymorphisms within the beta2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.
2012
Polymorphisms within the β2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reactionrestriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.
BMC Cardiovascular Disorders, 2008
Background The alpha1A-adrenergic receptor (α1A-AR) regulates the cardiac and peripheral vascular system through sympathetic activation. Due to its important role in the regulation of vascular tone and blood pressure, we aimed to investigate the association between the Arg347Cys polymorphism in the α1A-AR gene and blood pressure phenotypes, in a large sample of Brazilians from an urban population. Methods A total of 1568 individuals were randomly selected from the general population of the Vitória City metropolitan area. Genetic analysis of the Arg347Cys polymorphism was conducted by polymerase chain reaction/restriction fragment length polymorphism. We have compared cardiovascular risk variables and genotypes using ANOVA, and Chi-square test for univariate comparisons and logistic regression for multivariate comparisons. Results Association analysis indicated a significant difference between genotype groups with respect to diastolic blood pressure (p = 0.04), but not systolic blood...
American journal of …, 2004
Several case-control studies have explored the possible association between polymorphism in the  2 adrenoreceptor gene ( 2 AR), hypertension, and obesitythe focus being in particular on the Arg16Gly and Gln27Glu substitutions, which appear to modify the extracellular part of the  2 AR with possible functional modification. However, controversial results have been obtained. Design and Methods: The analysis refers to 993 middle-age men characterized for Arg16Gly and Gln27Glu polymorphism of the  2 AR. In this general population sample there were 563 overweight, 160 obese, and 405 hypertensive individuals, of whom 171 were receiving antihypertensive therapy. Results: The genotype frequencies for codon 16 were: GlyGly ϭ 38%; ArGly ϭ 45%; ArgArg ϭ 17%. The frequencies for codon 27 were: GlnGln ϭ 50%; GlnGlu ϭ 39%; GluGlu ϭ 11%. Codon 16 and codon 27 polymorphisms were in linkage disequilibrium. No differences were detected in body mass index and blood pressure across different genotypes. Likewise, no association was detected between either of the two polymorphisms and being overweight (codon 27: 2 ϭ 0.1, codon 16: 2 ϭ 1.4), obesity (codon 27: 2 ϭ 0.1, codon 16: 2 ϭ 1.7) and hypertension (codon 27: 2 ϭ 2.7, codon 16: 2 ϭ 1.9). The odds ratio (with 95% confidence intervals) for overweight, obesity, and hypertension were not different between genotypes. Likewise, no difference in the anthropometric indices of fat distribution, fasting blood glucose, serum insulin, triglycerides, uric acid, and HOMA index could be detected between groups. Conclusions: In summary, in this large unselected sample of adult white men, genetic variation in the  2 AR was not associated with blood pressure or with overweight, obesity, and fat distribution.