Article

Has pharmacogenetics brought us closer to 'personalized medicine' for initial drug treatment of hypertension?

Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0022, USA.
Current opinion in cardiology (Impact Factor: 2.59). 08/2009; 24(4):333-9. DOI: 10.1097/HCO.0b013e32832c58ba
Source: PubMed

ABSTRACT To describe recent advances in antihypertensive pharmacogenetics and discuss challenges related to translating this knowledge into 'personalized medicine' for the initial drug treatment of hypertension.
Recent studies included both prospective and retrospective analyses ranging from small clinical investigations of 42 participants to large, multicenter, randomized, outcome-based clinical trials of nearly 40 000 individuals. Treatment with drugs from five classes of antihypertensives was evaluated in these studies. The duration of treatment ranged from week-long follow up for blood pressure response to a decade-long follow up for clinical outcomes. In total, associations with 12 different candidate genes were assessed. These studies present the now familiar mixture of significant and nonsignificant pharmacogenetic findings that are sometimes consistent with, sometimes inconsistent with, previous findings in antihypertensive pharmacogenetics.
Recent research in antihypertensive pharmacogenetics has added to the existing evidence base, and novel genes and variants as well as new methodologies are cause for continued optimism. However, translation of genomic science to clinical settings has not kept pace with growing interest in personalized medicine for hypertension. New research paradigms may be needed to translate pharmacogenetics into clinical tools. Clinical application will also require a trained clinical workforce, validated genetic tests, and payers willing to fund pretreatment testing.

0 Bookmarks
 · 
130 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genes and environmental factors contribute to an individual's risk of hypertension. Recent advances in DNA sequencing technology have enabled the discovery of new causative genes in inherited forms of hypertension, identifying novel pathways for blood pressure control. Meta-analyses of genome-wide association studies have also identified regions of the genome that are significantly associated with blood pressure control, and these regions may be involved in an individual's response to antihypertensive medication. This article reviews the latest gene discoveries in inherited forms of hypertension, recent meta-analyses of genome-wide association studies, genetic determinants of antihypertensive therapy response, and development of genetic risk scores.
    Heart (British Cardiac Society) 03/2013; · 6.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective. To identify markers (phenotypic, genetic, or environmental) of blood pressure (BP) response profiles to angiotensin converting enzyme inhibitors (ACEIs) and diuretics. Methods. IDEAL was a crossover (two active and two wash out phases), double-blind, placebo-controlled trial. Eligible patients were untreated hypertensive, aged 25 to 70. After two visits, patients were randomized to one of four sequences. The main outcome was BP differences between the active treatment and placebo. Results. One hundred and twenty-four patients were randomised: mean age 53, men 65%, family history of hypertension 60%. Average BP fall at each visit before randomisation was about 2% of the initial level reflecting both a regression to the mean and a placebo effect. Conclusion. The results are expected to improve knowledge in drug's mechanisms of action and pathophysiology of hypertension, and to help in personalizing treatment. The estimation of BP responses to each drug in standardized conditions provided a benefit to each participant.
    Thérapie 05/2012; 67(3):195-204. · 0.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypertension affects approximately 1 billion people worldwide. Owing to population aging, hypertension-related cardiovascular burden is expected to rise in the near future. In addition to genetic variants influencing the blood pressure response to antihypertensive drugs, several genes encoding for drug-metabolizing or -transporting enzymes have been associated with blood pressure and/or hypertension in humans (e.g., ACE, CYP1A2, CYP3A5, ABCB1 and MTHFR) regardless of drug treatment. These genes are also involved in the metabolism and transport of endogenous substances and their effects may be modified by selected environmental factors, such as diet or lifestyle. However, little is currently known on the complex interplay between environmental factors, endogenous factors, genetic variants and drugs on blood pressure control. This review will discuss the respective role of population-based primary prevention and personalized medicine for arterial hypertension, taking a pharmacogenomics' perspective focusing on selected pharmacogenes.
    Expert Review of Clinical Pharmacology 11/2012; 5(6):677-86.