Pharmacogenetics of Antihypertensive Treatment: Detailing Disciplinary Dissonance

Abstract

Hypertension is a common condition associated with increased cardiovascular morbidity and mortality. In the USA only approximately a third of those who are aware of their hypertensive status successfully control their blood pressure. One reason for this is the unpredictable response individuals have to treatment. Clinicians must often rely on empirical methods to match patients with effective drug treatment. Hypertension pharmacogenetics seeks to find genetic predictors of response to drugs that lower blood pressure and to translate this knowledge into clinical practice. To date, around 60 studies have investigated associations between genetic polymorphisms and response to antihypertensive drugs. Here we review 18 studies that have been published since 2005. While consonant findings that are insufficient for clinical translation remain the norm, some consistent findings are emerging with several gene-treatment combinations. Nonetheless, differences in study designs, variable methods for assessing pharmacologic exposures, heterogeneous phenotypes (that is, response variables and outcomes ranging from blood pressure to clinical outcomes) and small sample sizes coupled with a short duration of follow-up in many studies account for a large portion of these inconsistencies. Progress in the future will depend upon our ability to launch large studies using high-fidelity phenotyping with multiple drugs and multiple ethnic groups.

Pharmacogenomic approaches to study the effects of antihypertensive drugs

“…Therefore, GWAS for pharmacogenomic studies of antihypertensive drugs is needed. 31 TARGET GENES RELATED TO PHARMACOKINETIC FUNCTION According to the review article 11 by Turner et al, most current studies in pharmacogenetics/pharmacogenomics of antihypertensive drugs are using candidate gene approaches to investigate receptors, enzymes and peptides related to physiologic blood pressure regulation, including those involved in the renin-angiotensin and sympathetic nervous systems, as well as those genes that regulate production of vasoactive substances and water-electrolyte metabolism. Other approaches to clarify the gene polymorphisms that increase responsiveness to antihypertensive drugs are to target mutations and polymorphisms in pharmacokinetic enzyme-associated genes.…”

Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients

“…Many drugs are effective in treating hypertension, although individuals can respond differently to the same drug. Interindividual variation in the efficacy of medications may be influenced by genetic variations [2][3][4] . Hypertension pharmacogenetics seeks to find genetic predictors of response to drugs that lower blood pressure.…”

Mutational analysis of the Kir6.1 gene in Chinese hypertensive patients treated with the novel ATP-sensitive potassium channel opener iptakalim

“…Hypertension pharmacogenetics seeks to find genetic predictors of response to drugs that lower blood pressure. More and more studies have investigated associations between genetic polymorphisms and response to drugs (3)(4)(5)(6).…”