الفهرس 
Ischemic Heart Disease
Clinical assessment, ECG and laboratory investigationsOnly 14 pages are availabe for public view
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Abstract
IHD is one of the most common causes of morbidity
and mortality worldwide. It is responsible for 47% of
deaths in Egypt. Ischemia of the myocardium emerges from
decreased oxygen supply in relation to demands. Currently,
atherosclerosis is the basis of IHD. Inflammation has a
major role in the pathogenesis of atherosclerosis.
Clinically, IHD presents either by ACS or CCS. It
may be asymptomatic, may manifest by stable or unstable
angina, acute myocardial infarction or sudden death.
Diagnosis of IHD is confirmed by ECG, elevated cardiac
markers and imaging techniques.
NO is a soluble gas with a very short half -life that is
synthesized and released in a continuous fashion in our
body and it is considered the most important molecule
produced by the vascular endothelium. It has many
activities that play a major role in vascular homeostasis
including vascular relaxation, inhibition of platelet and
leukocyte adhesion to the vascular wall and inhibition of
proliferation of smooth muscles. It is also protective against
atherosclerotic changes. Decreased NO activity facilitates
vascular inflammation and formation of foam cells.
Synthesis of NO is mediated by the action of an
enzyme NOS. It acts on Arginine to produce Citrulline and
NO. NOS enzyme has three isoforms; iNOS, nNOS and
eNOS. Endothelial NOS is mainly expressed in the
vascular endothelium, also detected in platelets and cardiac
muscles. Many environmental factors may affect eNOS
activity like cigarette smoking and aging.
NOS3 gene encodes the protein eNOS and is located
on the long arm of chromosome 7 and it is thought to play
an important role the in the pathogenesis of IHD. Individual
variations in NO production are explained by
polymorphism on the genetic level. The polymorphism of
interest in this study is a 27 base pair (bp) repeat in intron
4.
We conducted this study to assess the association
between intron 4a/b gene polymorphism and IHD among
smokers; it was a pilot study that included 60 subjects in
two groups.
The cases group included 30 subjects (15 smokers
and 15 non-smokers). Diagnosis of IHD was based on
history taking and performing coronary angiography that
showed the atherosclerotic coronaries and the extent of
atherosclerosis. The control group included 30 subjects (15
smokers and 15 non-smokers). The presence of IHD was
ruled out by taking history, ECG and echocardiography.
For both cases and controls group, the following data
were collected; family history of IHD, history of DM,
history of hypertension, lipid profile was assayed and
conventional PCR followed by gel electrophoresis was
done to detect eNOS intron 4a/b gene polymorphism using
whole blood EDTA samples.
Our results revealed higher frequency of DM and
hypertension among cases and this was statistically
significant. Additionally, smoking dose and triglyceride
level were significantly higher among cases group. We
compared the cases and the controls regarding the eNOS
LQWURQ DE JHQRW\SH IUHTXHQF\ DQG ZH GLGQ¶W ILQG
statistically significant difference (p-value= 0.522).
Although there was no statistically significant difference
between cases and controls regarding the genotype
frequency, 3 vessels significant occlusion was higher
among the ab/aa genotype group (p=value= 0.021).
Considering the a allele as the risky allele, we tried
to study its influence on the clinical data of both cases and
controls. The results revealed that family history of IHD
and hypertension in the cases group was significantly lower
among the a allele carrier group. Additionally, we tried to
assess the influence of the combined effect of smoking and
the presence of the a allele on incidence of IHD. The
results showed that presence of a DOOHOH GRHVQ¶W LQFUHDVH
risk of IHD among smokers.
Many studies were concerned in studying the
relationship between eNOS intron 4a/b gene polymorphism
and the risk of IHD; some confirmed the association and
others denied it. The different and conflicting conclusions
may arise from the different genetic susceptibility of the
different ethnic groups. Additionally, it is possible that
eNOS intron 4a/b gene polymorphism relation to IHD is
affected by linkage disequilibrium with other functional
variants in the gene regulatory regions.