Renin-angiotensin system gene polymorphisms and left ventricular hypertrophy. The case against an association

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.