Overview of the role of B2-adrenergic receptor variants in human hypertension (original) (raw)
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Polymorphism in the b 1 Adrenergic Receptor Gene and Hypertension
2010
Background—The Arg389 variant of the b1-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 for t...
Journal of hypertension, 2006
Objectives Current evidence demonstrates that both genetic and environmental factors influence blood pressure. The sympathetic nervous system is a key player in blood pressure control and functional genetic variants of the beta-2 adrenergic receptor (B2AR) have been identified and implicated in the pathogenesis of hypertension. The present study aimed to determine the effects of common haplotypes of the B2AR gene upon blood pressure in the Caerphilly Prospective Study.
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.
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...
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.
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.
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.
2005
Few studies have examined to what extent genetic variants of the  2-adrenoceptor (ADRB2) are involved in the development of hypertension with age, although  2-adrenergic receptor responsiveness declines in older subjects. To investigate this, 10 common single-nucleotide polymorphisms (SNPs) in the promoter and coding regions of the ADRB2 gene were genotyped in an unrelated population consisting of 2 ethnic groups: European American (EA; nϭ610) and African American (AA; nϭ420). ADRB2 haplotypes were estimated by expectation maximization (EM) algorithmbased methods. In the general population for EAs and AAs, the variants of the ADRB2 gene, including the individual SNPs and their haplotypes, were not associated with hypertension. However, there was a significant interaction between age and one of the common haplotypes (haplotype 1) in EAs (Pϭ0.01). Haplotype 1 was associated with protection against hypertension in young (Յ50 years of age) but not in old (Ͼ50 years of age) EAs (odds ratio, 0.5; 95% confidence interval, 0.27 to 0.91; Pϭ0.02). This age-specific effect was further supported by the observations that young subjects carrying Ն1 copy of haplotype 1 had significantly lower diastolic blood pressure and nearly 2-fold higher ADRB2 binding density than the noncarriers (PϽ0.05). With aging, their ADRB2 numbers decreased to the level of the noncarriers, along with increased body mass index (7%; PϽ0.05) and decreased heart rate (7%; PϽ0.001). Our study suggests that age is an important modifier for the effects of ADRB2 polymorphisms on ADRB2 function and the development of hypertension. (Hypertension. 2005;46:301-307.
β 2 -Adrenergic Receptor Gene Polymorphism, Age, and Cardiovascular Phenotypes
Hypertension, 2003
Previous studies suggest that variants of the β 2 -adrenergic receptor (ADRB2) may differently affect functional responses to adrenergic stimulation, thereby possibly modulating cardiovascular and metabolic phenotypes. We examined the hypothesis that G/R16 and Q/E27 polymorphism of ADRB2, or their haplotypes, may modulate blood pressure, cardiovascular structure, and function or metabolic cardiovascular risk factors in the general population. We examined a random sample of the general population (n=571; age, 35 to 64 years). Neither clinic nor 24-hour ambulatory blood pressure was significantly associated with ADRB2 genotypes in the overall population. Cardiac structure and function were also not influenced by ADRB2 polymorphism. After adjustment for potential confounders, association of the R16 allele with higher systolic blood pressure was observed in the subgroup of younger people (below age of 50 years). Haplotype analysis showed that higher blood pressure values were more speci...