1022-7954/02/3801- $27.00 © 2002
Russian Journal of Genetics, Vol. 38, No. 1, 2002, pp. 87–89. Translated from Genetika, Vol. 38, No. 1, 2002, pp. 105–107.
Original Russian Text Copyright © 2002 by Miloserdova, Slominsky, Limborska.
The angiotensin-converting enzyme (ACE) plays a
key role in the renin-angiotensin system. It converts the
inactive peptide angiotensin I into angiotensin II, a vas-
oconstrictor. In addition, ACE inactivates bradykinin
by converting it into inactive metabolites. Bradykinin is
an agent stimulating release of NO, the main endothe-
lial relaxation factor, by the endothelium. Thus, ACE is
crucial for maintenance of the equilibrium between
vasoconstrictors and vasodilators and, as a conse-
quence, for regulation of the vessel tone .
The level of ACE in the plasma of healthy people
can show individual variation. However, variability of
the parameter index in a given person is insigniﬁcant .
On these grounds, it has been suggested that individual
ACE levels are genetically determined.
In 1990, polymorphism of the gene for ACE was
found. It involves an insertion (I) or deletion (D) of 287
bp, containing an
repeat in the 16th intron. This
gave impetus to analysis of the association of this poly-
morphism with various diseases and the distribution of
various genotypes in populations. Analysis of ACE
level in blood plasma of individuals with different gen-
otypes demonstrated that homozygotes for the
had the highest ACE activity . However, data of dif-
ferent authors are controversial and do not provide clear
understanding of the role of this polymorphism in the
genesis of various diseases [4–8].
These differences can be at least partly explained by
the age-related dynamics of the ACE polymorphism
and change in the
allele frequencies [9–11]. We
have analyzed the insertion–deletion polymorphism for
the ACE gene in the following age groups.
(1) Senior adults (50 subjects, average age 83.17
3.39 years) surveyed in the 20th State Clinic of Mos-
cow in connection with various diseases;
(2) Middle-aged adults (100 subjects, average age
3.9 years) not selected for cardiovascular diseases.
(3) Young adults (50 individuals, average age 34.2
(4) Children (50 individuals, average age 2.9
Deoxyribonucleic acid has been isolated from lym-
phocytes of peripheral blood by conventional methods
on a 340A DNA extractor (Applied Biosystems). The
insertion–deletion polymorphism for the ACE gene has
been analyzed with standard primers  synthesized
at the Institute of Molecular Genetics, Russian Acad-
emy of Sciences. Each DNA sample was analyzed in at
least three replications . Statistical analysis of the
distribution of alleles and genotypes in the samples was
conducted using the
Mean frequencies of alleles and genotypes esti-
mated for each group are presented in the table and ﬁg-
ure. There is a trend toward an increase in the frequency
of the allele
and the genotype
and a decrease in
the frequency of the genotype
in the groups as their
average age increases. Signiﬁcant differences were
found between the allele composition in the two
extreme age groups (
< 0.05) and frequencies
of the genotype
in the group of children and the sec-
ond age group (
Thus, our results conﬁrm the increase in the fre-
homozygotes in the middle-aged group.
Age-Dependent Variation of the Allele and Genotype Frequencies
in Insertion–Deletion Polymorphism
for the Angiotensin-Converting Enzyme Gene
O. V. Miloserdova, P. A. Slominsky, and S. A. Limborska
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182 Russia
Received March 2, 2001; in ﬁnal form, April 26, 2001
—Insertion–deletion polymorphism of the gene for the angiotensin-converting enzyme has been
investigated in random samples from various age groups in the Moscow population. A statistically signiﬁcant
reduction in the insertion allele frequency has been found in senior age groups.
<10 35 55 >80
Age-related variation in the frequency of deletion allele
of the ACE gene in the Moscow population.