Pharmacogenomics of amlodipine and hydrochlorothiazide therapy and the quest for improved control of hypertension: a mini review.

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Johnson R, Dludla P, Mabhida S, Benjeddou M, Louw J, February F

Pharmacogenomics of amlodipine and hydrochlorothiazide therapy and the quest for improved control of hypertension: a mini review.

Heart Fail Rev. 2019 May;24(3):343-357. doi: 10.1007/s10741-018-09765-y.

PubMed ID

30645721 [ View in PubMed

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Abstract

Blood pressure (BP) is a complex trait that is regulated by multiple physiological pathways and include but is not limited to extracellular fluid volume homeostasis, cardiac contractility, and vascular tone through renal, neural, or endocrine systems. Uncontrolled hypertension (HTN) has been associated with an increased mortality risk. Therefore, understanding the genetics that underpins and influence BP regulation will have a major impact on public health. Moreover, uncontrolled HTN has been linked to inter-individual variation in the drugs' response and this has been associated with an individual's genetics architecture. However, the identification of candidate genes that underpin the genetic basis of HTN remains a major challenge. To date, few variants associated with inter-individual BP regulation have been identified and replicated. Research in this field has accelerated over the past 5 years as a direct result of on-going genome-wide association studies (GWAS) and the progress in the identification of rare gene variants and mutations, epigenetic markers, and the regulatory pathways involved in the pathophysiology of BP. In this review we describe and enhance our current understanding of how genetic variants account for the observed variability in BP response in patients on first-line antihypertensive drugs, amlodipine and hydrochlorothiazide.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Levamlodipine	Voltage-dependent L-type calcium channel subunit alpha-1C	Protein	Humans	Unknown	Antagonist	Details
Levamlodipine	Voltage-dependent L-type calcium channel subunit alpha-1D	Protein	Humans	Unknown	Antagonist	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Levamlodipine	P-glycoprotein 1	Protein	Humans	Unknown	Substrate	Details