PECAM-1 GENE POLYMORPHISM (rs668) AND SUBCLINICAL
MARKERS OF CAROTID ATHEROSCLEROSIS IN PATIENTS
WITH TYPE 2 DIABETES MELLITUS
Popović D, Nikolajević Starčević J, Šantl Letonja M, Makuc J,
Cokan Vujkovac A, Reschner H, Bregar D, Petrovič D
*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: 63
|
|
DISCUSSION
In the present study, we demonstrated an association
between the rs668 GG genotype and carotid
artery plaque incidence in patients with T2DM when
adjusted to other risk factors. On the other hand, we
did not find any effect of the rs688 genotype on the
progression of atherosclerosis in patients with T2DM.
Our study is the first demonstrating an association
between the rs668 PECAM-1 and the presence of
carotid plaques in patients with T2DM. In our study,
we observed a greater number of plaques in subjects
with the GG rs668 genotype. The importance of the
PECAM-1 gene in the pathogenesis of atherosclerosis
was demonstrated [21,25]. The decrease in areas with
atherosclerotic lesion in PECAM-1 double knock-out
mice was reported [21,25].
An association between the rs668 PECAM-1 and
car-diovascular disorders was reported several times,
but not in all studies [29-33]. Similarly, an association
between the rs668 PECAM-1 gene and either the
increased levels of soluble PECAM-1 or ischemic
stroke was found in the Chinese population [21]. An
association between the rs668 PECAM-1 gene and
increased levels of soluble PECAM-1 was confirmed
in the setting of patients with acute MI [28].
Similarly, Fang et al. [29] demonstrated an association
between the rs668 PECAM-1 gene and either
increased levels of soluble PECAM-1 or the severity
of coronary artery disease in the Asian Indian population
in Singapore. Reschner et al. [17] reported an
association between the PECAM-1 rs668 (the CC
genotype) and MI in Caucasians with T2DM. Finally,
the effect of several polymorphisms of the PECAM-1
gene on cardiovascular disease was confirmed by
Listi et al. [30] in the Northern Italian population.
These findings were not confirmed in the general
population from Germany, as rs688 was not found
to be an independent risk factor for coronary artery
disease (CAD) [31].
In a recently published meta-analysis of 15 studies,
including 7636 subjects, no association between
the rs668 PECAM-1 and cardiovascular diseases was
demonstrated [35]. Moreover, the progression of subclinical
markers of carotid atherosclerosis was statistically
significantly faster in subjects with T2DM
in comparison with subjects without T2DM. This
finding is in accordance with expectations of other
researchers as well [32,33].
Our study has some limitations due to its actual
design (cross-sectional design at the enrollment of
subjects with T2DM and control subjects) and relatively
small sample size (i.e., less than 1000 subjects
with T2DM), however the study was appropriately
powered to detect the differences in subclinical markers
of carotid atherosclerosis upon enrollment as well
as during follow-up. The lack of the effect of rs688
on the progression of atherosclerosis might be due to
a rather short interval between the first and control
examinations (3.8 ± 0.5 years). Moreover, it is impossible
to exclude the impact of interactions with other potentially relevant variables on the development of
atherosclerosis. The second limitation of the study
is the lack of an intermediate phenotype, i.e., serum
PECAM levels. We presume that the effect of rs668
is via increased serum PECAM levels.
In conclusion, our study demonstrated a minor
effect of the rs668 PECAM-1 on the markers of carotid
atherosclerosis in subjects with T2DM, as the
GG genotype of the rs668 PECAM-1 was associated
with a higher incidence of carotid plaques in subjects
with T2DM. With that kind of associations established
in genetic studies, we presumed that we might
predict the genetic risk of carotid atherosclerosis in
subjects with T2DM.
|
|
|
|
 |
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 |
|
|
