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Advancing management of hypertension through pharmacogenomics.

ABSTRACT: Hypertension is the most common, chronic disease in the world, and there are many effective pharmacological agents available for its treatment. Despite the plethora of treatment options, data across the globe suggest that blood pressure control rates are < 50%, a fact likely influenced in part by the inability to predict the antihypertensive drug likely to be most effective for an individual patient. Pharmacogenomics in hypertension holds the promise of identifying genetic biomarkers for antihypertensive drug response, which might be used in the future in treatment selection. Research in the field is also likely to enhance our understanding of hypertension and the mechanisms by which the various drugs produce efficacy. There are several examples in the literature of genes with relatively strong data on associations of genetic polymorphisms with antihypertensive response; the data on ADRB1, CACNB2, and NEDD4L are detailed as examples. Substantial additional data in hypertension pharmacogenomics are expected to be forthcoming from recently completed genome-wide association studies. Increased collaboration among research groups will help insure successful discoveries from these large-scale studies. The next decade should clearly define the potential clinical implications of the research in hypertension pharmacogenomics that is currently in progress.

SUBMITTER: Johnson JA

PROVIDER: S-EPMC3686275 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Advancing management of hypertension through pharmacogenomics.

Johnson Julie A JA

Annals of medicine 20120601

Hypertension is the most common, chronic disease in the world, and there are many effective pharmacological agents available for its treatment. Despite the plethora of treatment options, data across the globe suggest that blood pressure control rates are < 50%, a fact likely influenced in part by the inability to predict the antihypertensive drug likely to be most effective for an individual patient. Pharmacogenomics in hypertension holds the promise of identifying genetic biomarkers for antihyp ...[more]

PMID: 22713143

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Project description:Pulmonary arterial hypertension (PAH) is a rare disease with heterogeneous causes that can lead to right ventricular (RV) failure and death if left untreated. There are currently 10 medications representative of five unique pharmacologic classes that are approved for treatment. These have led to significant improvements in overall clinical outcome. However, substantial variability in dosing requirements and treatment response is evident, leading to suboptimal outcome for many patients. Furthermore, dosing is empiric and iterative and can lead to delays in meeting treatment goals and burdensome adverse effects. Pharmacogenomic (PGx) associations have been reported with certain PAH medications, such as treprostinil and bosentan, and can explain some of the variability in response. Relevant genes associated with treprostinil include CYP2C8, CYP2C9, CAMK2D, and PFAS. CYP2C8 and CYP2C9 are the genes encoding the major metabolizing liver enzymes for treprostinil, and reduced function variants (*2, *3) with CYP2C9 were associated with lower treatment persistence. Additionally, a higher CYP2C9 activity score was associated with a significantly less risk of treatment discontinuation. Other genes of interest that have been explored with treprostinil include CAMK2D, which is associated with right ventricular dysfunction and significantly higher dose requirements. Similarly, PFAS is associated with lower concentrations of cyclic adenosine monophosphate and significantly higher dose requirements. Genes of interest with the endothelin receptor antagonist (ERA) class include GNG2 and CYP2C9. A genetic variant in GNG2 (rs11157866) was linked to a significantly increased rate of clinical improvement with ERAs. The *2 variant with CYP2C9 (encoding for the major metabolizing enzyme for bosentan) was significantly associated with a higher risk for elevations in hepatic aminotransferases and liver injury. In summary, this article reviews the relevant pharmacogenes that have been associated to date with dosing and outcome among patients who received PAH medications.

Dataset Information

Advancing management of hypertension through pharmacogenomics.

Publications

Advancing management of hypertension through pharmacogenomics.

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