Genetics of blood pressure hypertensive complications, and antihypertensive drug responses

Stephen T Turner, Eric Boerwinkle

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Hypertension is the most prevalent, treatable risk factor for diseases of the heart, brain and kidneys. In this review, we discuss advances in understanding of the genetics of blood pressure regulation, the development of hypertensive complications and the pharmacodynamics of antihypertensive drug responses. Discovery of single gene mutations that cause hypertension or hypotension in humans suggests that the common final pathway for regulation of blood pressure level is via alterations in renal sodium handling. Based on a working hypothesis that common genetic variations contributing to blood pressure variation in the population may also act on this same pathway, we summarize supporting evidence emerging from linkage and selected association studies of candidate genes - including those encoding components of the renin-angiotensin-aldosterone system, the epithelial sodium channel, adrenoceptors, G protein subunits, and other cellular signaling mediators and modifiers. We proceed to distinguish ischemic target organ complications due to arteriolosclerotic changes of the microvasculature from those due to atherosclerosis involving larger conduit and capacitance arteries. Using the example of subcortical white matter ischemia of the brain, we propose that interindividual variation in the arteriolosclerotic complications is more likely than atherosclerotic complications to be related to the same genetic (and environmental) mechanisms that contribute to hypertension. We conclude by summarizing the state-of-the-art of antihypertensive pharmacogenetics, which has succeeded in rejecting the null hypothesis that genetic variation does not influence blood pressure or protective target organ responses to drug therapy. In each of the three areas covered in this review, we indicate the many remaining obstacles to the routine clinical use of genetic measurements in the diagnosis, evaluation and treatment of hypertension.

Original languageEnglish (US)
Pages (from-to)53-65
Number of pages13
JournalPharmacogenomics
Volume4
Issue number1
DOIs
StatePublished - Jan 2003

Fingerprint

Antihypertensive Agents
Blood Pressure
Hypertension
Genetic Association Studies
Epithelial Sodium Channels
Pharmacogenetics
Protein Subunits
Kidney Diseases
Brain Diseases
Renin-Angiotensin System
Microvessels
Brain Ischemia
GTP-Binding Proteins
Hypotension
Adrenergic Receptors
Heart Diseases
Atherosclerosis
Arteries
Sodium
Kidney

Keywords

  • Blood pressure
  • Genetics
  • Hypertension
  • Pharmacology
  • Target organ disease

ASJC Scopus subject areas

  • Pharmacology
  • Genetics(clinical)

Cite this

Genetics of blood pressure hypertensive complications, and antihypertensive drug responses. / Turner, Stephen T; Boerwinkle, Eric.

In: Pharmacogenomics, Vol. 4, No. 1, 01.2003, p. 53-65.

Research output: Contribution to journalArticle

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