ACE genotype and ACE inhibitor response in kidney disease: a perspective.
Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce blood pressure and slow the progression of renal diseases. However, a substantial interindividual variability in treatment response also has been noted. The activity of ACE is partially dependent on the presence or absence of a 287-bp element in intron 16, and this insertion/deletion (I/D) polymorphism accounts for 47% of the total phenotypic variance in plasma ACE; DD subjects have the highest; ID subjects, intermediate; and II individuals, the lowest concentrations. Data suggest that genotype also determines tissue enzyme activity, and, at least under certain conditions, ACE activity is a rate-limiting step for angiotensin II formation. It therefore has been speculated that the ACE polymorphism also might affect therapeutic effects of ACE inhibitors. Unfortunately, clinical studies performed to date do not allow us to draw definite conclusions. Nonetheless, the rapidly evolving area of pharmacogenomics soon will also affect therapeutic decisions in the field of nephrology and hypertension.
Mayer
Gert
G
Division of Nephrology, University of Innsbruck, Austria. gert.mayer@uibk.ac.at
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics* / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A