There is substantial evidence to suggest that BP (blood pressure) is an inherited trait. The introduction of gene technologies in the late 1980s generated a sharp phase of over-inflated prospects for polygenic traits such as hypertension. Not unexpectedly, the identification of the responsible loci in human populations has nevertheless proved to be a considerable challenge. Common variants of the RAS (renin–angiotensin system) genes, including of ACE (angiotensin-converting enzyme) and AGT (angiotensinogen) were some of the first shown to be associated with BP. Presently, ACE and AGT are the only gene variants with functional relevance, where linkage studies showing relationships with hypertension have been reproduced in some studies and where large population-based and prospective studies have demonstrated these genes to be predictors of hypertension or BP. Nevertheless, a lack of reproducibility in other linkage and association studies has generated scepticism that only a concerted effort to attempt to explain will rectify. Without these explanations, it is unlikely that this knowledge will translate into the clinical arena. In the present review, we show that many of the previous concerns in the field have been addressed, but we also argue that a considerable amount of careful thought is still required to achieve enlightenment with respect to the role of RAS genes in hypertension. We discuss whether the previously identified problems of poor study design have been completely addressed with regards to the impact of ACE and AGT genes on BP. In the context of RAS genes, we also question whether the significance of ‘incomplete penetrance’ through associated environmental, phenotypic or physiological effects has been duly accounted for; whether appropriate consideration has been given to epistatic interactions between genes; and whether future RAS gene studies should consider variation across the gene by evaluating ‘haplotypes’.
Skip Nav Destination
Article navigation
Review Article|
January 26 2010
Gene variants of the renin–angiotensin system and hypertension: from a trough of disillusionment to a welcome phase of enlightenment?
Gavin R. Norton;
Gavin R. Norton
1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa
Search for other works by this author on:
Richard Brooksbank;
Richard Brooksbank
1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa
Search for other works by this author on:
Angela J. Woodiwiss
1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa
Correspondence: Professor Angela J. Woodiwiss (e-mail: angela.woodiwiss@wits.ac.za).
Search for other works by this author on:
Clin Sci (Lond) (2010) 118 (8): 487–506.
Article history
Received:
September 29 2009
Revision Received:
November 25 2009
Accepted:
December 03 2009
Citation
Gavin R. Norton, Richard Brooksbank, Angela J. Woodiwiss; Gene variants of the renin–angiotensin system and hypertension: from a trough of disillusionment to a welcome phase of enlightenment?. Clin Sci (Lond) 1 April 2010; 118 (8): 487–506. doi: https://doi.org/10.1042/CS20090498
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.