1022-7954/03/3902- $25.00 © 2003
Russian Journal of Genetics, Vol. 39, No. 2, 2003, pp. 229–235. Translated from Genetika, Vol. 39, No. 2, 2003, pp. 293–299.
Original Russian Text Copyright © 2003 by Aitkhozhina, Lyudvikova.
The last 15 years have witnessed great progress in
research of genes responsible for the predisposition to
cardiovascular diseases. The most probable candidates
for this role are at least 50 genes from different groups,
such as genes for lipid metabolism, vascular proteins,
for the proteins regulating vascular reactions (vaso-
constrictors and vasodilators), genes of hemostatic
The renin-angiotensin system (RAS) is known to
signiﬁcantly contribute to the development of coronary
heart diseases, including serious complications of car-
diovascular diseases, such as myocardial infarction and
cerebral thrombosis. The main RAS components are
genes of angiotensinogen, renin, angiotensin-convert-
ing enzyme (ACE), and type I vascular receptor of
angiotensin II . Protein products of these genes reg-
ulate the balance between vasoconstriction factors.
Angiotensinogen undergoes modiﬁcation by means of
enzymes (peptidases), namely, renin and ACE,
which leads to the occurrence of angiotensinogen
II. The latter is in turn the main vasoconstrictor act-
ing by itself or as a stimulator of many secretory hor-
mones, (aldosterone, a regulator of water–salt
metabolism, and vasopressin) .
To date, 31 cases of angiotensinogen polymorphism
have been described, eight of which are signiﬁcant and
lead to amino acid substitution, six are synonymic, and
17 are located in untranslated regions . Among them,
two polymorphisms involving mutations in the second
exon are studied in most detail. These are nucleotide
substitutions that lead to substitutions of threonine with
methionine in the 235 position (M235T) and of threo-
nine with methionine in the 174 position (T174M) of
amino acid sequence [4, 5]. In addition, it was found
that a highly polymorphic dinucleotide repeat (CA)
located in the 3'-untranslated region of the angiotensi-
nogen gene . This microsatellite was analyzed, and
13 allelic variants of the repeat were identiﬁed .
Sequence analysis of the ATG gene promoter region
revealed another polymorphism in the –6 position .
These polymorphisms were shown to be associated
with cardiovascular diseases . Undoubtedly, ATG
polymorphism in most cases is related to different car-
diovascular diseases, especially to hypertension, which
can be easily explained considering that angiotensino-
gen has a direct effect on the level of blood pressure.
Polymorphism of the angiotensinogen gene promoter
region is little studied and the functional role of this
polymorphism has not yet been determined .
The enzyme ACE is also one of the main compo-
nents of the renin–angiotensin system involved in the
water–salt (sodium) homeostasis of the human organ-
ism. This enzyme belongs to carboxypeptidases and is
responsible for the excision of the C-terminal dipeptide
from angiotensin I and its conversion to angiotensin II,
the main factor of vasoconstriction that causes the con-
striction of blood vessels . Angiotensin-converting
enzyme also participates in the degradation of bradyki-
nine, indirectly elevating arterial hypertension. Hence,
an increased ACE activity must lead to functional dis-
orders in the cardiovascular system .
In this connection, we studied polymorphism of the
promoter region of the angiotensinogen gene (ATG)
and an insertion/deletion polymorphism of the 16th
intron of the gene for angiotensin-converting enzyme in
the ethnic group of Kazakhs.
Polymorphism of the Promoter Region of the Angiotensinogen
Gene and the Gene for Angiotensin I-Converting Enzyme
in Arterial Hypertension and Cardiovascular Disease
of the Kazakh Ethnic Group
N. A. Aitkhozhina and E. K. Lyudvikova
Aitkhozhin Institute of Molecular Biology and Biochemistry, National Academy of Sciences of Kazakhstan,
Almaty, 480012 Kazakhstan; fax: (7-3272) 921-947; e-mail: email@example.com
Received October 4, 2002
—Polymorphism of the promoter region of the angiotensinogen gene (ATG) and an angiotensin I-con-
verting enzyme gene (ACE) insertion/deletion (I/D) polymorphism were studied in three different groups of
Kazakhs (control group, patients with cardiovascular disease (CAD) and patients with arterial hypertension
(AH)) using three methods. A comparative analysis of the distribution of genotype and allele frequencies was