Ueda S, Meredith P, Morton JJ, Connell JMC, Elliot H
The insertion deletion polymorphism of the human ACE gene
differentiates the response to enalaprilat in normotensive
males
16th Scientific Meeting of the International Society of Hypertension
ISH Abstract Book
(Jun) 16: 1996
The I/D polymorphisms in intron 16 of the ACE gene is associated with
variability in plasma ACE levels - the D allele is associated with
higher ACE. However, whether this polymorphism has physiological
relevance is unresolved.
This paper compares the response to infused Ang I, before and after
enalaprilat (0.01mg/kg), in 12 normal DD homozygotes and 11 normal II
homozygotes. The ACE inhibitor caused more prolonged inhibition of the
pressor actions of Ang I in the II homozygotes.
Comment: This is one of the first demonstrations of a
functional role for the I/D polymorphism - and has some clinical
relevance in that DD homozygotes may require higher doses of ACEi.
Genetic markers in candidate genes must be studied in this way to
determine whether the polymorphisms are functional; similar data are
needed for all genetic association studies on candidate genes
(Alan Jardine, M.D., Glasgow University, Scotland).
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16th Scientific Meeting of the International Society of Hypertension
H: Pathophysiology :
Genetics
H: Drug therapy :
ACE inhibitors