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
|
|
DISCUSSION
In this study, we demonstrated the effect of the
DD genotype of the rs4646994 (ACE I/D) polymorphism
on atherosclerosis progression in subjects with
T2DM. Statistically significant differences in a 3.8-
year observation period were found in the change in
the sum of carotid plaques for the rs4646994 polymorphism.
Our findings are in accordance with the
findings of Saitou et al. [5], who on a cohort of 222 T2DM patients reported faster progression of atherosclerosis
in subjects with the D allele.
Moreover, in our study, we did not demonstrate
an association between tested polymorphisms
(rs4646994, rs4341) and either CIMT or CIMT progression
in an almost 4-year period. In 1994, it was
reported for the first time that ACE levels correlate
with CIMT in healthy persons [6]. As the ACE I/D
polymorphism is known to affect circulating ACE
levels (subjects with the DD genotype having the
highest serum ACE levels compared to subjects with
other genotypes) [7], subsequent studies have already
been conducted to identify a possible association
of the ACE I/D genotype with atherosclerosis,
both on general and diabetic populations, providing
contradictory results [5-10]. Using smaller or larger
cohorts of the general population, association of the
ACE I/D polymorphism with carotid atherosclerosis
was confirmed in some studies [6-8] and opposed by
others [9]. Finally, large meta-analyses confirmed
statistically significant association of ACE I/D with
CIMT in the general population [10].
In studies that did not focus on the general population
but on patients with T2DM, Kogawa et al.
[11] in 1997, studied femoral and CIMT in healthy
persons and patients with T2DM, and showed that
only in T2DM patients was there a significant association
of the D allele with higher CIMT. Since the
study of Kogawa et al. [11], studies focusing on the
association of CIMT and the ACE I/D polymorphism
provided contradictory results, similar to studies conducted
in the general population. In the diabetic heart
study no association was found between ACE I/D
and CIMT [12], similar to the study focusing on the
offspring of patients with T2DM [13]. On the other
hand, Sticchi et al. [14] reported a higher risk of
carotid stenosis in D allele carriers, and Zhou et al.
[15] reported higher lipid levels in older patients with
T2DM carrying the D allele, which could promote
atherosclerosis progression.
Certain limitations of our study should be noted.
First is the moderate sample size of our study.
However, all the participants were enrolled from an
ethnically homogenous population, which minimizes
possible biases from population stratification. Second,
the results of our study may be affected by statin
therapy, and antihypertensive agents, and these facts
were not appreciated in the statistical analysis.
In conclusion, our study represents the first larger
study focusing on the effect of two ACE polymorphisms
(rs4646994 and rs4341) on the progression
of carotid atherosclerosis in subjects with T2DM. We
demonstrated that those subjects with T2DM with
the DD genotype of the rs4646994 (ACE I/D) polymorphism
had faster progression of atherosclerosis
in comparison with subjects with other genotypes.
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
