الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
Coronary artery disease (CAD) is the leading cause of death worldwide
and is characterized by the accumulation of atheromatous plaques within the
walls of the coronary arteries. CAD is a multifactorial disease influenced by
genetic and environmental factors for which hypertension, smoking, diabetes
mellitus, dyslipidemia, obesity and family history are important risk factors
contributing to the occurrence of the disease.
Experimental and clinical studies demonstrated that the human
angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene
polymorphism of 287bp in intron 16 and a polymorphism arising from
methionine to therionine (M>T) substitution in position 235 of the coded
protein (M235T) in the angiotensinogen (AGT) gene as the main components of
rennin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and
prognosis of CAD.
Interleukin-18 (IL-18) is a pro-inflammatory cytokine that strongly
induces the formation of plaques in patients with CAD, and variations in IL-18
gene promoter polymorphism at positions (607C/A) and (137G/C) found to
influence IL-18 level and clinical outcomes among individuals with heart
disease.
The aim of this study was to evaluate the level of IL-18 as a proinflammatory
cytokine and to investigate the genotype distribution and the
allele frequencies ofthe two IL-18 promoter gene polymorphisms at positions (-
607C/A) and (-137G/C), ACE (I/D) and AGT (M235T) and their potential
association with coronary artery disease in Egyptian population.
The study was carried out on 170 Egyptian individuals; all patients
(n=120) selected fromthe National Heart Institute, Giza, Egypt.
The studied populationswere classified into three groups:
group (Ι) (CAD group):
This group consisted of 60 patients(40 males and 20 females) and their
ages ranged from 32 to 69 years who were documented CAD.
group (Π) (Non-CAD group):
This group consisted of 60 patients(27 males and 33 females) and their
ages ranged from 27 to 72 years who were documented free CAD, they suffered
from CAD risk factors like (diabetes, hypertension, obesity, smoking and
dyslipidemia).
group (ΙΙΙ) (Control group):
This group consisted of 50 healthy subjects (37 males and 13 females)
and their ages ranged from 25 to 55 years,they were age- sex matched with
patients and they free from any disease that interfere with this study.
All groups will be subjected to:
Full history and clinical examinations will be done to exclude other
cardiovascular diseases.
Research Investigations included:
Determination of serum lipid profile (Total Cholesterol, Triglyceride and
HDL-Cholesterol) by enzymatic colorimetric assay.
The LDL-Cholesterol concentrations were determined using the Friedwald
formula.
Determination of human seruminterleukin-6 (IL-6) and interleukin-18 (IL-
18) levels by ELISA technique.
Detection ofAngiotensin converting enzyme (ACE) gene insertion/deletion
(I/D) polymorphism using polymerase chain reaction(PCR) amplification.
Detection of Angioteninogen (AGT) gene M235T polymorphism using
polymerase chain reaction restriction fragment length polymorphism
(PCR-RFLP) method.
Detection of the two Interleukin-18 (IL-18) promoter gene polymorphisms
at positions (-607C/A) and (-137G/C) using polymerase chain reactionspecific
sequence primer (PCR-SSP)method.
The results of the study can be summarized as follows:
Regarding IL-18 promoter gene polymorphism at positions (607C/A) and
(137G/C); our results indicated that there was a significant association
between the wild GG genotype and/or the G allele of the (137G/C) IL-18
promoter variant in patients with CAD, whereas there was no significant
association between the (607C/A) IL-18 promoter variant in CAD, non-
CAD groups compared to the control group.
The results showed that there was a significant association between the
IL-18 (137G/C) gene polymorphism and both of lipid profiles (total
cholesterol, triglyceride and LDL-C) and gender in CAD group.
Regarding the ACE (I/D) gene polymorphism, our data indicated that
there was a significant association between the mutant DD genotype
distribution and D allele frequencies in CAD group.
The data showed that there was a significant association between ACE
(I/D) gene polymorphism and serum level of IL-6, triglyceride and LDLC
in CAD group.
For AGT (M235T) gene polymorphism, our findings revealed that there
was a significant association between the mutant TT genotype
distribution and T allele frequency in CAD group.
The results found that there was a significant association betweenAGT
(M235T) gene polymorphismand serum level of IL-6.
The present study reported that the ACE-DD/AGT-TT combined
genotype was significantly higher in patients with CAD than patients
without CAD with marked increase to disease occurrence.
The results revealed that the ACE-DD/IL-18(607)-AA/IL-18(137)-
GGcombined genotype was significantly higher in patients with CAD
than patients without CAD. Moreover, there was non-significant
differences in the interaction between IL-18(607C/A)/IL-
18(137G/C)/AGT (M235T).
Our results indicated that a significant increase in lipid parameters such as
cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and a
significant decrease in high density lipoprotein (HDL) in CAD
patients.Also, a positive association of TC/HDL-C ratio in CAD patients
was observed.
The data showed that there was a significance association of gender,
aortic root (AR) and right ventricle (RV) in CAD patients.
Our results indicated that there was a significant increase in serum
Interleukin-6 (IL-6) and Interleukin-18 (IL-18) levels in patients with
CAD.