Bruno Baudin
Angiotensin I-Converting Enzyme Gene Polymorphism and Drug Response
An insertion/deletion (I/D) polymorphism of the angiotensin
I-converting enzyme (ACE) gene has been
described in chromosome 17q23 of the human
genome. Subjects with the genotype DD have
markedly higher plasma ACE levels than those with
genotype II; although ACE concentration in plasma is
not rate-limiting for the production of angiotensin II, it
has been suggested that the renin-angiotensin system
may have an enhanced role in cardiovascular homeostasis
in subjects with DD genotype or D allele. Metaanalysis
confirmed the association of the D allele with
an increased risk of myocardial infarction and stroke,
but these relations are still uncertain with longevity
and renal deterioration. Otherwise, I allele seems to be
related with an improved response to physical training.
The I/D polymorphism of the ACE gene is not a
marker for any form of hypertension, though some
conflicting results have been described. Nevertheless
this polymorphism may have an influence on the antihypertensive
response, particularly when using ACE
inhibitors (ACEI). For example, blood pressure normalization
with captopril in patients suffering from cardiac
failure would be more effective in II genotype;
conversely, both regression in left ventricular hypertrophy
and improvement in diastolic filling would be
greater after long-term treatment with enalapril in patients
with essential hypertension and DD genotype.
Conflicting results were also described using ACEI as a
renoprotective therapy. This review therefore supports
the justification for further evaluation in appropriately
powered studies.
Clinical Chemical Laboratory Medicine, Walter de Gruyter
Print ISSN: 1434-6621
Volume: 38, 09/2000
Pages: 853 - 856
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