Renin-angiotensin system gene polymorphisms: potential mechanisms for their association with cardiovascular diseases

Since the first description of the angiotensin-converting enzyme insertion/ deletion polymorphism more than a decade ago, many hundreds of investigatio ns have reported associations between this polymorphism and cardiovascular diseases. Subsequently, similar studies were performed in relationship with several other renin-angiotensin system gene polymorphisms, most notably th e angiotensinogen M235T polymorphism and the angiotensin AT, receptor A1166 C polymorphism. Surprisingly however, especially in view of the many contra dictory results that have been obtained, very little attention has been pai d to the mechanism(s) that may link these genetic variants and respective d iseases. Here, we review the limited evidence that is currently available o n the functional consequences (including compensatory mechanisms) of the ab ove three renin-angiotensin system gene polymorphisms, in order to provide an explanation for the reported associations (or lack thereof) between thes e polymorphisms and cardiovascular diseases. (C) 2000 Elsevier Science B.V. All rights reserved.