The Genetic Basis of Essential Hypertension and Its Implications for Treatment

  • K. M. O’Shaughnessy
  • M. R. Wilkins
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 160)

Abstract

Hypertension is an asymptomatic condition but a major risk factor for cardiovascular events and stroke. Blood pressure exhibits a skewed normal distribution in the general population with no natural hypertensive threshold. Decisions regarding who to treat and with what drugs are based upon morbidity and mortality data in large population studies, the presence/absence of co-existing disease and cost. Because of variation between individuals in their response to antihypertensive drugs, patients are frequently exposed to a number of different drugs before a suitable agent (or combination of agents) is found. This increases the potential for adverse drug reactions and/or poor compliance. A few patient characteristics can be used to help predict their blood pressure response to a drug such as age, race and perhaps renin levels. Genetic factors also influence the level of blood pressure in an individual, susceptibility to target organ damage and the response to antihypertensive drugs. Genes with a large influence on blood pressure have been identified for rare familial forms of hypertension, but these account for a very small fraction of the general hypertensive population. Their elucidation has helped define pathophysiological pathways and suggests new biochemical factors for further genetic studies or drug targeting. The hunt is on for genes which influence blood pressure in a much larger proportion of the population. The broader vision is that knowledge of a patient’s genotype coupled with epidemiological and clinical data can help in tailoring therapy to the individual patient. How useful it turns out to be will ultimately depend upon whether blood pressure is regulated by a relatively small number of genes with significant effects or a large number of genes with very small effects.

Keywords

Hypertension Candidate genes Animal models Target organ damage 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • K. M. O’Shaughnessy
    • 1
  • M. R. Wilkins
    • 2
  1. 1.Clinical Pharmacology Unit, Level 6, Addenbrooke’s Centre for Clinical InvestigationAddenbrooke’s HospitalCambridgeUK
  2. 2.Faculty of Medicine, Imperial College of Science, Technology and MedicineHammersmith CampusLondonUK

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