CARDIOVASCULAR JOURNAL OF AFRICA • Volume 25, No 1, January/February 2014
AFRICA
9
Endothelial function and germ-line
ACE
I/D,
eNOS
and
PAI-1
gene profiles in patients with coronary slow flow
in the Canakkale population: multiple thrombophilic
gene profiles in coronary slow flow
Emine Gazi, Ahmet Temiz, Burak Altun, Ahmet Barutcu, Fatma Silan, Yucel Colkesen, Ozturk Ozdemir
Abstract
Background:
We examined the effects of
ACE
,
PAI-1
and
eNOS
gene polymorphisms on endothelial function. The
genes are related to atherosclerosis and endothelial dysfunc-
tion in coronary slow flow (CSF).
Methods:
Thirty-three patients with angiographically proven
CSF and 48 subjects with normal coronary flow were enrolled
in this study. Coronary flow patterns were determined by the
thrombolysis in myocardial infarction (TIMI) frame count
method. Endothelial function was assessed in the brachial artery
by endothelium-dependent flow-mediated dilatation (FMD).
PAI-1
4G/5G,
eNOS
T-786C and
ACE
I/D polymorphisms were
determined by polymerase chain reaction (PCR) amplification.
Results:
No difference was found between the groups regarding
age, heart rate and blood pressure. Males were more prevalent
among patients with CSF than control subjects (58.8 vs 29.8%,
p
=
0.009). Mean TIMI frame counts were significantly higher
in CSF patients (24.2
±
4.0 vs 13.1
±
2.5 fpm,
p
=
0.001). FMD
was significantly lower in CSF patients than in the controls (4.9
±
6.6 vs 7.9
±
5.6%,
p
=
0.029). TIMI frame count and FMD
were found to be negatively correlated in a correlation analysis
(
r
=
–0.269,
p
=
0.015).
PAI-1
4G/5G,
eNOS
T-786C and
ACE
I/D polymorphisms were similar in the two groups.
Conclusions:
This study showed that endothelial function was
impaired in patients with CSF.
PAI-1
,
ACE
and
eNOS
poly-
morphisms were not related to CSF in our study population.
Keywords:
thrombophilic genes, SNP, PAI-1 4G/5G, eNOS
T-786C, ACE I/D, coronary slow flow
Submitted 26/7/13, accepted 22/11/13
Published online 16/1/14
Cardiovasc J Afr
2014;
25
: 9–14
DOI: 10.5830/CVJA-2013-083
Coronary slow flow (CSF) was first reported in 1972 as an
angiographic phenomenon, described as delayed passage of
angiographic contrast agent along the coronary arteries in the
absence of stenosis in the epicardial vessels.
1
CSF is relatively
rare, more frequently seen in young men and smokers with
recurrent chest pain. Some cases of sudden cardiac death have
been reported in patients with CSF.
2
It was thought to be due
to coronary microvascular endothelial dysfunction and diffuse
atherosclerosis, although the aetiopathogenesis is unclear.
3,4
Flow-
mediated dilatation (FMD) is a simple, non-invasive, repetitive
method for assessment of endothelial function.
5
Impaired FMD
has been reported in CSF patients.
6
The angiotensin converting enzyme (ACE) is part of the renin–
angiotensin system and plays an important role in haemostasis of
the vascular wall.
7
Regulation of the activity of ACE in both
the circulation and tissues is under the control of the
ACE
gene
located on chromosome 17q23. The
ACE
gene has an insertion/
deletion (I/D) polymorphism in the non-coding region of the
gene.
8
Serum ACE activity is higher in subjects with deletion/
deletion (D/D) alleles than in subjects with I and D alleles and
is related to hypertension and cardiovascular disease.
8,9
The
frequency of the DD genotype and D allele was reported to be
higher in SCF patients.
10,11
Nitric oxide (NO) is synthesised from L-arginine by nitric
oxide synthase and has an effect on endothelial relaxation.
12
NO plays a protective role in atherogenesis, and deficiency
in NO activity causes coronary spasms.
13
A polymorphism of
endothelial NO synthase (
eNOS
) is located on chromosome
7q35-56 and influencesNOproduction. Nakayama
et al
. originally
reported a mutation of thymidine, being replaced by cytosine at
the nucleotide -786 (T-786C) gene.
14
This polymorphism, which
results in a significant reduction in eNOS gene promoter activity,
is associated with hypertension, acute coronary syndrome and
coronary vasospasm.
15-19
Tissue plasminogen activator inhibitor 1 (PAI-1) plays an
important role in endogenous fibrinolytic activity. Recent
studies demonstrated that elevated PAI-1 activity was related to
atherosclerosis, and was an independent predictor of coronary
artery disease and myocardial infarction.
20,21
The
PAI-1
gene is
located on 7q21.3-22 and polymorphism of the 4G/5G gene is
located in the
PAI-1
gene promoter region. The fifth guanine
(G) base is inserted or deleted in the 4G sequence in the 675th
base of the initial transcription point upstream. The
PAI-1
gene
has three genotypes, namely, 4G/4G, 4G/5G and 5G/5G. 4G/4G
allele carriers always have higher plasma PAI-1 activity than
4G/5G and 5G/5G carriers.
22
The aim of this study was to investigate the association
between
ACE
I/D,
eNOS
and
PAI-1
gene polymorphisms and
endothelial function, evaluated by FMD, in patients with CSF.
Department of Cardiology, Faculty of Medicine, Canakkale
Onsekiz mart University, Canakkale, Turkey
Emine Gazi, MD,
Ahmet Temiz, MD
Burak Altun, MD
Ahmet Barutcu, MD
Yucel Colkesen, MD
Department of Medical Genetics, Faculty of Medicine,
Canakkale Onsekiz Mart University, Canakkale, Turkey
Fatma Silan, MD
Ozturk Ozdemir, MD
