Pharmacogenomic studies of hypertension

Paving the way for personalized antihypertensive treatment

Michael Eadon, Sri H. Kanuri, Arlene B. Chapman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Introduction: Increasing clinical evidence supports the implementation of genotyping for anti-hypertensive drug dosing and selection. Despite robust evidence gleaned from clinical trials, the translation of genotype guided therapy into clinical practice faces significant challenges. Challenges to implementation include the small effect size of individual variants and the polygenetic nature of antihypertensive drug response, a lack of expert consensus on dosing guidelines even without genetic information, and proper definition of major antihypertensive drug toxicities. Balancing clinical benefit with cost, while overcoming these challenges, remains crucial. Areas covered: This review presents the most impactful clinical trials and cohorts which continue to inform and guide future investigation. Variants were selected from among those identified in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR), the Genetic Epidemiology of Responses to Antihypertensives study (GERA), the Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study, the SOPHIA study, the Milan Hypertension Pharmacogenomics of hydrochlorothiazide (MIHYPHCTZ), the Campania Salute Network, the International Verapamil SR Trandolapril Study (INVEST), the Nordic Diltiazem (NORDIL) Study, GenHAT, and others. Expert Commentary: The polygenic nature of antihypertensive drug response is a major barrier to clinical implementation. Further studies examining clinical effectiveness are required to support broadbased implementation of genotype-based prescribing in medical practice.

Original languageEnglish (US)
Pages (from-to)33-47
Number of pages15
JournalExpert Review of Precision Medicine and Drug Development
Volume3
Issue number1
DOIs
StatePublished - Jan 3 2018

Fingerprint

Antihypertensive Agents
Hypertension
trandolapril
Pharmacogenetics
Genotype
Clinical Trials
Hydrochlorothiazide
Molecular Epidemiology
Diltiazem
Verapamil
Drug-Related Side Effects and Adverse Reactions
Cost-Benefit Analysis
Pharmacogenomic Testing
Guidelines
Pharmaceutical Preparations

Keywords

  • Antihypertensive
  • Blood pressure
  • Implementation
  • Pharmacogenomics
  • Precision medicine

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Molecular Medicine
  • Genetics

Cite this

Pharmacogenomic studies of hypertension : Paving the way for personalized antihypertensive treatment. / Eadon, Michael; Kanuri, Sri H.; Chapman, Arlene B.

In: Expert Review of Precision Medicine and Drug Development, Vol. 3, No. 1, 03.01.2018, p. 33-47.

Research output: Contribution to journalArticle

@article{945bfc3e46cb479488b8c3549e49db95,
title = "Pharmacogenomic studies of hypertension: Paving the way for personalized antihypertensive treatment",
abstract = "Introduction: Increasing clinical evidence supports the implementation of genotyping for anti-hypertensive drug dosing and selection. Despite robust evidence gleaned from clinical trials, the translation of genotype guided therapy into clinical practice faces significant challenges. Challenges to implementation include the small effect size of individual variants and the polygenetic nature of antihypertensive drug response, a lack of expert consensus on dosing guidelines even without genetic information, and proper definition of major antihypertensive drug toxicities. Balancing clinical benefit with cost, while overcoming these challenges, remains crucial. Areas covered: This review presents the most impactful clinical trials and cohorts which continue to inform and guide future investigation. Variants were selected from among those identified in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR), the Genetic Epidemiology of Responses to Antihypertensives study (GERA), the Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study, the SOPHIA study, the Milan Hypertension Pharmacogenomics of hydrochlorothiazide (MIHYPHCTZ), the Campania Salute Network, the International Verapamil SR Trandolapril Study (INVEST), the Nordic Diltiazem (NORDIL) Study, GenHAT, and others. Expert Commentary: The polygenic nature of antihypertensive drug response is a major barrier to clinical implementation. Further studies examining clinical effectiveness are required to support broadbased implementation of genotype-based prescribing in medical practice.",
keywords = "Antihypertensive, Blood pressure, Implementation, Pharmacogenomics, Precision medicine",
author = "Michael Eadon and Kanuri, {Sri H.} and Chapman, {Arlene B.}",
year = "2018",
month = "1",
day = "3",
doi = "10.1080/23808993.2018.1420419",
language = "English (US)",
volume = "3",
pages = "33--47",
journal = "Expert Review of Precision Medicine and Drug Development",
issn = "2380-8993",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

TY - JOUR

T1 - Pharmacogenomic studies of hypertension

T2 - Paving the way for personalized antihypertensive treatment

AU - Eadon, Michael

AU - Kanuri, Sri H.

AU - Chapman, Arlene B.

PY - 2018/1/3

Y1 - 2018/1/3

N2 - Introduction: Increasing clinical evidence supports the implementation of genotyping for anti-hypertensive drug dosing and selection. Despite robust evidence gleaned from clinical trials, the translation of genotype guided therapy into clinical practice faces significant challenges. Challenges to implementation include the small effect size of individual variants and the polygenetic nature of antihypertensive drug response, a lack of expert consensus on dosing guidelines even without genetic information, and proper definition of major antihypertensive drug toxicities. Balancing clinical benefit with cost, while overcoming these challenges, remains crucial. Areas covered: This review presents the most impactful clinical trials and cohorts which continue to inform and guide future investigation. Variants were selected from among those identified in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR), the Genetic Epidemiology of Responses to Antihypertensives study (GERA), the Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study, the SOPHIA study, the Milan Hypertension Pharmacogenomics of hydrochlorothiazide (MIHYPHCTZ), the Campania Salute Network, the International Verapamil SR Trandolapril Study (INVEST), the Nordic Diltiazem (NORDIL) Study, GenHAT, and others. Expert Commentary: The polygenic nature of antihypertensive drug response is a major barrier to clinical implementation. Further studies examining clinical effectiveness are required to support broadbased implementation of genotype-based prescribing in medical practice.

AB - Introduction: Increasing clinical evidence supports the implementation of genotyping for anti-hypertensive drug dosing and selection. Despite robust evidence gleaned from clinical trials, the translation of genotype guided therapy into clinical practice faces significant challenges. Challenges to implementation include the small effect size of individual variants and the polygenetic nature of antihypertensive drug response, a lack of expert consensus on dosing guidelines even without genetic information, and proper definition of major antihypertensive drug toxicities. Balancing clinical benefit with cost, while overcoming these challenges, remains crucial. Areas covered: This review presents the most impactful clinical trials and cohorts which continue to inform and guide future investigation. Variants were selected from among those identified in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR), the Genetic Epidemiology of Responses to Antihypertensives study (GERA), the Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study, the SOPHIA study, the Milan Hypertension Pharmacogenomics of hydrochlorothiazide (MIHYPHCTZ), the Campania Salute Network, the International Verapamil SR Trandolapril Study (INVEST), the Nordic Diltiazem (NORDIL) Study, GenHAT, and others. Expert Commentary: The polygenic nature of antihypertensive drug response is a major barrier to clinical implementation. Further studies examining clinical effectiveness are required to support broadbased implementation of genotype-based prescribing in medical practice.

KW - Antihypertensive

KW - Blood pressure

KW - Implementation

KW - Pharmacogenomics

KW - Precision medicine

UR - http://www.scopus.com/inward/record.url?scp=85053444667&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053444667&partnerID=8YFLogxK

U2 - 10.1080/23808993.2018.1420419

DO - 10.1080/23808993.2018.1420419

M3 - Article

VL - 3

SP - 33

EP - 47

JO - Expert Review of Precision Medicine and Drug Development

JF - Expert Review of Precision Medicine and Drug Development

SN - 2380-8993

IS - 1

ER -