The Association of ADRB1 and CYP2D6 Polymorphisms With Antihypertensive Effects and Analysis of Their Contribution to Hypertension Risk

Chen, Liping; Xiao, Ting; Chen, Liling; Xie, Shanshan; Deng, Maoqing; Wu, Dingchang

doi:10.1016/j.amjms.2017.11.002

Cited by 18 publications

(12 citation statements)

References 20 publications

(31 reference statements)

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“…Consistent with some previous reports, we did not find a better BP response to the β-Blocker in individuals homozygous for either the ADRB1 Arg389Gly or Ser49Gly polymorphisms (36,37). However, a recent study reported that patients with the ADRB1 homozygous form showed a better response to metoprolol compared with those harboring the heterozygous variant (38). Suonsyrja et al (36) reported that patients with the Gly389Gly genotype tended to better BP response to bisoprolol than those with Arg389Arg genotypes and no significant difference was found.…”

Section: Discussionsupporting

confidence: 90%

Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension

Zeng

Chu

et al. 2022

Front. Cardiovasc. Med.

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PurposeThis study examined the effects of plasma renin activity (PRA), angiotensin II (Ang II) and aldosterone (PAC) concentrations as well as common polymorphisms in the β1-Adrenoceptor gene (ADRB1) and the G-protein α-Subunit (Gαs) protein gene the G protein α-Subunit 1 gene (GNAS) on the blood pressure (BP) and heart rate (HR) response to bisoprolol in Chinese patients with hypertension.MethodsPatients with sitting clinic systolic BP (SBP) 140–169 mmHg and/or diastolic BP (DBP) 90–109 mmHg after placebo run-in were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Patients diagnosed as having primary aldosteronism or renal artery stenosis were excluded. PRA, Ang II and PAC concentrations were measured after the placebo run-in and after 6 weeks of treatment. The Ser49Gly and Arg389Gly polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS were genotyped by the TaqMan® assay.ResultsIn 99 patients who completed the study, baseline PAC levels were significantly associated with baseline DBP and plasma potassium on univariate but not on multivariate linear regression analysis. PRA, Ang II, and PAC concentrations at baseline were not associated with changes in BP with bisoprolol treatment, but the values were all significantly reduced (PRA −0.141 ± 0.595 ng/mL/h, Ang II −2.390 ± 5.171 pmol/L and aldosterone −51.86 ± 119.1 pg/mL; all P < 0.05) following 6 weeks of bisoprolol treatment. There were no significant differences in BP or HR responses in patients with baseline PRA above or below the PRA cut-point of 0.65 ng/mL/h or the median value of 0.9 ng/ml/hour. There were no significant associations of the ADRB1 and GNAS polymorphisms with the clinic and ambulatory BP and HR responses to bisoprolol.ConclusionBaseline PRA, PAC and Ang II concentrations showed no significant association with the BP response to bisoprolol treatment, but all these parameters were reduced after 6 weeks of treatment with bisoprolol. The two common polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS had no significant association with the BP and HR response to bisoprolol in these patients.

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Section: Discussionsupporting

confidence: 90%

Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension

Zeng

Chu

et al. 2022

Front. Cardiovasc. Med.

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“…Similar results were also found in Chinese hypertensive patients treated with the β‑blocker carvedilol 50. In the opposite direction, Chen et al recently reported that subjects carrying the Gly/Gly genotype for Arg389Gly polymorphism show greater antihypertensive responses to metoprolol 51. Regardless of these positive findings, lack of association between Ser49Gly or Arg389Gly polymorphisms and blood pressure responses to β-blockers was reported in two European prospective studies 52,53…”

Section: β-Blockerssupporting

confidence: 53%

“…Regardless of these positive findings, lack of association between Ser49Gly or Arg389Gly polymorphisms and blood pressure responses to β-blockers was reported in two European prospective studies 52,53Table 2Summary Of Studies On The Pharmacogenomics Of β-BlockersGenePolymorphismStudy TypeStudy PopulationMain FindingsReference ADRB1 rs1801253Candidate geneCaucasian (n=29), African American (n=10) and Hispanic (n=1) populationArg/Arg genotype carrier have better blood pressure responses to metoprolol49 ADRB1 rs1801253Candidate geneChinese population (n=86)Arg/Arg genotype carriers have better blood pressure responses to carvedilol50 ADRB1 rs1801253Candidate geneChinese population (n=261)Gly/Gly genotype carriers have greater antihypertensive responses to metoprolol51 ADRB1 rs1801252Candidate geneCaucasians (n=233)Ser49Ser homozygotes showed a non-significant tendency to have a better response to bisoprolol52 ADRB1 rs1801253 or rs1801252Candidate geneCaucasians (n = 340)There was no association of the polymorphisms with the blood pressure response to atenolol53 CYP2D6 *4Candidate geneCaucasians (n= 1533)* 4/4 * genotype carriers have better blood pressure responses to metoprolol57 CYP2D6 *3, *4, othersCandidate geneCaucasians (n=84)There was association of the polymorphisms with the blood pressure response to metoprolol58 CYP2D6 *2,*3, othersCandidate geneAfrican Americans (n=84), European Americans (n=125), A...…”

Section: β-Blockersmentioning

confidence: 96%

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Oliveira-Paula

Pereira

Tanus‐Santos

et al. 2019

PGPM

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Hypertension is a multifactorial disease that affects approximately one billion subjects worldwide and is a major risk factor associated with cardiovascular events, including coronary heart disease and cerebrovascular accidents. Therefore, adequate blood pressure control is important to prevent these events, reducing premature mortality and disability. However, only one third of patients have the effective control of blood pressure, despite several classes of antihypertensive drugs available. These disappointing outcomes may be at least in part explained by interpatient variability in drug response due to genetic polymorphisms. To address the effects of genetic polymorphisms on blood pressure responses to the antihypertensive drug classes, studies have applied candidate genes and genome wide approaches. More recently, a third approach that considers gene-gene interactions has also been applied in hypertension pharmacogenomics. In this article, we carried out a comprehensive review of recent findings on the pharmacogenomics of antihypertensive drugs, including diuretics, β-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and calcium channel blockers. We also discuss the limitations and inconsistences that have been found in hypertension pharmacogenomics and the challenges to implement this valuable approach in clinical practice.

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“…How to prescribe the most effective antihypertensive drugs with the least amount of side effects for each hypertensive patient is a major issue for clinicians. It has been found that the heterogeneity of patients' responses to antihypertensive drugs is, to a large extent, genetically determined (12)(13)(14). However, personalized pharmacotherapy based on genetic information has not yet been established in the field of hypertension research.…”

Section: Discussionmentioning

confidence: 99%

Personalized antihypertensive treatment guided by pharmacogenomics in China

Xiao¹,

Yang²,

Chen³

et al. 2022

Cardiovasc Diagn Ther

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Background: The implementation of genotyping for anti-hypertensive drugs in clinical practice remains a challenge. We conducted this study to analyze the distribution of polymorphisms of antihypertensive drugrelated genes in Changsha County in China and compare the clinical effectiveness of genotype-guided and clinical experience-guided antihypertensive therapy in hypertensive individuals.Methods: A total of 9,933 essential hypertensive participants from Changsha County were consecutively enrolled in our study, and 7 genetic polymorphic loci (CYP2D6*10, ADRB1, CYP2C9*3, AGTR1, ACE, CYP3A5*3 and NPPA) were detected by a polymerase chain reaction (PCR)-fluorescence probe. From an available sample of 660 hypertensive participants, 495 cases were randomly identified by genotype-guided therapy and 165 cases by clinical experience-guided therapy. We performed 24-hour ambulatory blood pressure (BP) monitoring on each of these cases, pre-and post-intervention.Results: In the enrolled 9,933 cases, the mutation frequencies of CYP2C9*3, ADRB1(1165G>C), AGTR1(1166A>C), CYP2D6*10, ACE(I/D), CYP3A5*3 and NPPA(2238T>C) were 4.41%, 74.60%, 5.55%, 57.08%, 30.94%, 69.03% and 1.19%, respectively. In both genotype-guided and clinical experience-guided groups, the comparisons of intra-group pre-and post-treatments showed significant decreases in diastolic blood pressure (DBP) (P<0.01) and significant increases in the control rate of BP (47.1% vs. 38.6% and 37.5% vs. 33.9%, P<0.05) in response to adjusted antihypertensive agents. Correspondingly, the extent of the reduction of systolic blood pressure (SBP; 3.52±11.72 vs. 0.92±9.14 mmHg), the extent of the increase in the rate of BP control (8.5% vs. 3.6%) and the percentage rate of decrease of grades 2 and 3 hypertensive individuals were more significant in the genotype-guided group than that in the clinical experience-guided group (P<0.01).Conclusions: While prescribing anti-hypertensive drugs, appropriate dosage and type adjustments should be made according to the gene mutation frequency and individual circumstances. Pharmacogenomics-guided personalized treatment of hypertensive patients is likely to be a more effective strategy, especially in those with significantly elevated SBP.

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The Association of ADRB1 and CYP2D6 Polymorphisms With Antihypertensive Effects and Analysis of Their Contribution to Hypertension Risk

Cited by 18 publications

References 20 publications

Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension

Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension

<p>Pharmacogenomics And Hypertension: Current Insights</p>

Personalized antihypertensive treatment guided by pharmacogenomics in China

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