ASSOCIATION OF THE ACE rs4646994 AND rs4341
POLYMORPHISMS WITH THE PROGRESSION
OF CAROTID ATHEROSCLEROSIS IN SLOVENIAN
PATIENTS WITH TYPE 2 DIABETES MELLITUS
Merlo S1, Novák J2,3,4, Tkáčová N2, Nikolajević Starčević J5, Šantl Letonja M6, Makuc J7,
Cokan Vujkovac A7, Letonja J5, Bregar D5, Zorc M5, Rojko M5, Mankoč S5, Kruzliak P8, Petrovič D5
*Corresponding Author: Professor Daniel Petrovič, M.D., Ph.D., Institute of Histology and Embryology, Faculty
of Medicine University Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia. Tel: +386-1-543-7367. Fax: +386-1-
543-7361. E-mail: daniel.petrovic@mf.uni-lj.si
page: 37
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INTRODUCTION
Type 2 diabetes mellitus (T2DM) represents a
chronic illness characterized by the disability of the
body to utilize glucose either because of insulin resistance
in peripheral tissues or because of a decreased
production of insulin by the pancreas [1]. Type 2
diabetes mellitus is known to promote the atherosclerotic
process, which is characterized by endothelial
dysfunction and by accumulation of foam cells and
vessel wall inflammation. As the process continues,
the narrowing of the vessel lumen occurs, leading to
acute cardiovascular events [2].
The renin-angiotensin-aldosterone system is
one of the main regulators of blood pressure having
also other local (tissue-specific) roles [3]. Genetic
polymorphisms in different parts of this system have
previously been described to associate with various
cardiovascular and other diseases, with the angiotensin-converting-enzyme (ACE) insertion/deletion
(I/D) polymorphism representing one of the most
commonly studied polymorphisms that affects circulating
ACE levels [3]. This polymorphism has recently
been shown to be in linkage disequilibrium
with another ACE polymorphism, rs4341 [3]; however,
data about these two polymorphism and their
possible association with carotid atherosclerosis in
patients with diabetes mellitus are limited.
The present study was thus designed to investigate
the association between polymorphisms of the
ACE gene (rs 4646994 and rs4341) and markers of
carotid atherosclerosis [carotid intima media thickness
(CIMT), number of affected segments of carotid
arteries and sum of plaques thickness] in patients
with T2DM. The second aim was to see whether
these two polymorphisms (rs4646994 and rs4341) affect
progression of carotid atherosclerosis in a 4-year
follow-up.
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