Renin-Angiotensin System Gene Polymorphisms and Left Ventricular Hypertrophy
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There is accumulating evidence for association between genetic polymorphisms of components of the renin angiotensin system (RAS), especially angiotensin-converting enzyme (ACE), and cardiovascular disease. However, there is lack of agreement that the ACE polymorphism is associated with left ventricular hypertrophy (LVH) in hypertension. A possible paradigm for the development of LVH involves the ACE gene polymorphism influencing cardiac mass by an action on plasma and/or tissue levels of angiotensin II. Such a model has experimental support and provides the basis for examining the lack of agreement between studies. The finding of lack of association between RAS gene polymorphism and LVH may be due to methodological problems, differences in genetic background between populations, interactions between genetic variants of RAS components or to the model being inappropriate.
Low predictability of ACE genotype markers for LVH together with conflicting reports on the influence of RAS genetic variants on angiotensin II production suggests that the simple RAS paradigm may not apply for hypertension. Further information on the nature of the link between the ACE polymorphism and ACE regulation as well as the relation between the RAS and pathophysiology of LVH is needed. At present there is insufficient evidence to accept ACE gene polymorphism as a susceptibility marker for LVH.
KeywordsLeft Ventricular Hypertrophy Renin Angiotensin System Total Wall Thickness Prince Charles Hospital Renin Angiotensin System Component
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- 1.Cambien F, Poirier O, Lecerf L, Evans A, Cambou J-P, Arveiler D, Luc G, Bard J-M, Bara L, Ricard S, Tiret L, Amouyet P, Alhenc-Gelas F, Soubrier F. Deletion polymorphism in the gene for angiotensin-con-verting enzyme is a potent risk factor for myocardial infarction. Nature 1992;359:641–644.PubMedCrossRefGoogle Scholar
- 12.Dzau VJ, Sasamura H, Hein L. Heterogeneity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications. J Hyptertens 1993; 11Suppl 3:S13–8.Google Scholar
- 14.Klickstein LB, Kaempfer CE, Wintraub BU. The granulocyte-angiotensin system. Angiotensin 1-converting activity of cathepsin. G. J. Biol Chem 1982;257:15042–6.Google Scholar
- 15.Tang SS, Loscalzo J, Dzau VJ. Tissue plasminogen activator activates renin angiotensin in vitro. J Vasc Med Biol 1989;1:67–74.Google Scholar
- 17.Montgomery H, Clarkson P, Dollery C, Prasad K, Losi M-A, Statters D, Jubb M, McEwan J, Humphries S, McKenna W. D polymorphism of the angiotensin-converting enzyme gene is strongly associated with the development of physiological left ventricular hypertrophy. (Abstract.) J Am Coll Cardiol 1996;27(Suppl A):244A.Google Scholar
- 20.Lindpaintner K, Lee M, Larson MG, Rao S, Pfeffer MA, Ordovas JM, Schaefer EJ, Wilson AF, Wilson PWF, Vasan RS, Myers RH, Levy D. Absence of association or genetic linkage between angiotensin-converting enzyme gene and left ventricular mass. N Engl J Med 1996;334:1023–1028.PubMedCrossRefGoogle Scholar
- 24.West MJ, Wong KK, Summers KM, Burstow DJ. Inability to demonstrate association between markers of angiotensinogen or angiotensin-converting enzyme in hypertensive subjects with different phenotypes of cardiac hypertrophy (abstract). 7th Europ Meeting on Hypertension 1995, P206.Google Scholar