Candidate Genes in the Pharmacogenomics of Antihypertensive Treatment - A Review and Future Aspects

P.      Hallberg; H.      Melhus

Abstract

Diversity in response to antihypertensive therapy is well-documented. Among many variables in the biological system, reasons include the genetic make-up of individuals. Although individual human genomes are 99.9% identical, the 0.1% difference predicts as many as three million polymorphisms. Some will affect protein expression or function, resulting in phenotypes affected for disease or with altered drug response. Pharmacogenomics focuses on the link between polymorphism in genes and variable response to drugs. The genetic approach to the study of the mechanisms underlying hypertension has led to the identification of some quantitative trait loci or genes that influence blood pressure regulation. An ultimate goal of pharmacogenomic knowledge is to advance beyond the current approach to antihypertensive drug therapy to more individualized approaches. Drugs that are more specific for the molecular characteristics of individual patients should contribute to greater efficacy and reduced toxicity. In this article, we review the pathophysiology of essential hypertension, the principles of its drug treatment, and those pharmacogenomic studies of antihypertensive treatment which, to our knowledge, have been published so far and which deals primarily with two aspects: the blood pressure lowering effect and the regression of left ventricular hypertrophy. Also, a selection of functional polymorphisms in potential candidate genes which have not yet appeared in pharmacogenomic studies of antihypertensive treatment but in various ways have been linked to hypertension and / or its related diseases / organ damages are discussed.

Keywords: polymorphisms, hypertrophy, hypertension, blood pressure, pharmacogenomic

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