Impact of CYP2D6 Polymorphisms on Clinical Efficacy and Tolerability of Metoprolol Tartrate

Hamadeh, Issam; Langaee, Taimour; Dwivedi, R.; García, S. Gómez; Burkley, Ben; Skaar, Todd C.; Chapman, Arlene B.; Gums, John G.; Turner, Stephen T.; Gong, Yan; Cooper‐DeHoff, Rhonda M.; Johnson, Julie A.

doi:10.1038/clpt.2014.62

Cited by 90 publications

(103 citation statements)

References 24 publications

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“…Indeed, the emphasis of this review has been on drug efficacy and agent selection. However, there is significant evidence supporting variants predicting adverse events including the hyperuricemia of thiazide use 94 , bradycardia associated with β-blockers [5][6][7][8]95,96 , and ACEI-related cough 97 .…”

Section: Methodsmentioning

confidence: 99%

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A Physiologic Approach to the Pharmacogenomics of Hypertension

Eadon

Chapman

2016

Advances in Chronic Kidney Disease

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Section: Methodsmentioning

confidence: 99%

“…However, a prospective, double-blind, longitudinal study of metoprolol use found significant differences in diastolic BP (DBP), QT interval, heart rate, and incidence of bradycardia 6,7 . As such, the Dutch pharmacogenomics working group (DPWG) has endorsed CYP2D6 screening with the use of metoprolol 8 .…”

Section: Metabolism Polymorphismsmentioning

confidence: 99%

A Physiologic Approach to the Pharmacogenomics of Hypertension

Eadon

Chapman

2016

Advances in Chronic Kidney Disease

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“…Details regarding enrollment criteria have been previously published, and the studies are registered at clinicaltrials.gov (PEAR, NCT00246519; PEAR2, NCT01203852). 14,15 In both studies, male or female patients 17-65 years of age, of any race or ethnicity, with uncomplicated HTN were included. Study participants were excluded if they had complicated HTN, DM (or fasting blood glucose ‡ 126 mg/dL) or documented CVD (including history of angina pectoris, heart failure, cardiac pacemaker, myocardial infarction, stroke, etc.…”

Section: Pear Studiesmentioning

confidence: 99%

Association of Branched and Aromatic Amino Acids Levels with Metabolic Syndrome and Impaired Fasting Glucose in Hypertensive Patients

Weng

Quinlivan

Gong

et al. 2015

Metabolic Syndrome and Related Disorders

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Background: The three branched amino acids (valine, leucine, and isoleucine) and two aromatic amino acids (tyrosine and phenylalanine) have been associated with many adverse metabolic pathways, including diabetes. However, these associations have been identified primarily in otherwise healthy Caucasian populations. We aimed to investigate the association of this five-amino-acid signature with metabolic syndrome and impaired fasting glucose (IFG) in a hypertensive cohort of Caucasian and African Americans. Methods: We analyzed data from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) studies PEAR and PEAR2 conducted between 2005 and 2014. Subjects were enrolled at the University of Florida (Gainesville, FL), Emory University (Atlanta, GA), and Mayo Clinic (Rochester, MN). A total of 898 patients with essential hypertension were included in this study. Presence of metabolic syndrome and IFG at baseline were determined on the basis of measurements of demographic and biochemical data. Levels of the five amino acids were quantified by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Results: With a multiple logistic regression model, we found that all five amino acids were significantly associated with metabolic syndrome in both Caucasian and African Americans. IFG and the five amino acids were associated in the Caucasian Americans. Only valine was significantly associated with IFG in African Americans. Conclusion: In both Caucasian and African Americans with uncomplicated hypertension, plasma levels of the five-amino-acid signature are associated with metabolic syndrome. Additionally, in Caucasians we have confirmed the five-amino-acid signature was associated with IFG.

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“…The PEAR-2 study was a multicenter sequential monotherapy clinical trial (clinicaltrials.gov identifier NCT01203852) 12 evaluating genetic determinants of BP response to metoprolol monotherapy and chlorthalidone monotherapy. Both PEAR-1 and PEAR-2 studies included individuals with mild to moderate essential hypertension.…”

Section: Methodsmentioning

confidence: 99%

Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans

et al. 2016

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African Americans suffer a higher prevalence of hypertension compared to other racial/ethnic groups. In this study, we performed a pharmacogenomics genome-wide association study of blood pressure response to β-blockers in African Americans with uncomplicated hypertension. Genome-wide meta-analysis was performed in 318 African American hypertensive participants in the two Pharmacogenomic Evaluation of Antihypertensive Responses studies: 150 treated with atenolol monotherapy and 168 treated with metoprolol monotherapy. The analysis adjusted for age, gender, baseline BP and principal components for ancestry. Genome-wide significant variants with p < 5*10−8 and suggestive variants with p < 5*10−7 were evaluated in an additional cohort of 141 African Americans treated with the addition of atenolol to hydrochlorothiazide treatment. The validated variants were then meta-analyzed in these 3 groups of African Americans. Two variants discovered in the monotherapy meta-analysis were validated in the add-on therapy. African American participants heterozygous for SLC25A31 rs201279313 deletion vs wild-type genotype had better diastolic blood pressure response to atenolol monotherapy, metoprolol monotherapy and atenolol add-on therapy: −9.3 vs. −4.6, −9.6 vs. −4.8 and −9.7 vs. −6.4 mmHg, respectively (3-group meta-analysis p= 2.5*10−8, beta = −4.42 mmHg per variant allele). Similarly, LRRC15 rs11313667 was validated for systolic blood pressure response to β-blocker therapy with 3-group meta-analysis p = 7.2 *10−8 and beta = −3.65 mmHg per variant allele. In this first pharmacogenomics genome-wide meta-analysis of BP response to β-blockers in African Americans, we identified novel variants that may provide valuable information for personalized antihypertensive treatment in this group.

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Impact of CYP2D6 Polymorphisms on Clinical Efficacy and Tolerability of Metoprolol Tartrate

Cited by 90 publications

References 24 publications

A Physiologic Approach to the Pharmacogenomics of Hypertension

A Physiologic Approach to the Pharmacogenomics of Hypertension

Association of Branched and Aromatic Amino Acids Levels with Metabolic Syndrome and Impaired Fasting Glucose in Hypertensive Patients

Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans

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