الفهرس 
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Abstract
Coronary Artery Disease (CAD) will be the leading cause of death in developing countries by the year 2020. In Egypt, mortality secondary to CAD is rapidly rising. According to WHO statistics the age-standardized mortality rates from CAD are one of the highest worldwide.
Angiotensin II, The major component of the RAS is involved in blood pressure hemostasis and cardiovascular pathophysiology. Two isoforms of endothelial receptors for angiotensin II are known so far: AT1 and AT2. The receptors belong to the superfamily of the G-protein-coupled receptors. Most of their physiological effects are mediated by the activation of AT1 subtype receptors.
The aim of our work is to study the association between the A1675G genetic polymorphism of AT2R gene and susceptibility to acute myocardial infarction and to correlate the genotypic results to the severity of the coronary artery disease and to the different risk factors such as smoking, diabetes, hypertension, hyperlipidemia and family history of CAD.
This study was done at Medical Biochemistry Department, Faculty of Medicine, Ain Sham University during the period from 2011 – 2013.
It included 70 male patients. They were stratified into 2 groups:
group A: patients with acute myocardial infarction (n= 35).
group B: individuals with chest pain and conventional risk factors for myocardial infarction served as a control group (n=35).
As regards the age of myocardial infarction patients, they aged between 44 and 86 years at the time of diagnosis (mean age 59.5±8.35 years) while in control individuals, They aged between 39 and 69 years at the time of diagnosis (mean age 56.2±11.28 years).
All patients in the present study were subjected to complete detailed history taking, general and local examination, routine laboratory investigations and group A patients were subjected to coronary angiography for assessment of severity of the coronary artery disease.
Five ml of venous blood were withdrawn from each participant. The blood was divided into two tubes: Ethylene Diamine Tetraacetic acid (EDTA) sterile vacutainer tubes for DNA extraction and the other portion was put in plain tubes & then the serum was stored -80C for estimation of serum lipid profile.
PCR RFLP was done on all samples using the appropriate primers. The PCR product was then digested with the HPY188III restriction enzyme. Replacement of an A (adenine) by a G (Guanine) created a new restriction site for the enzyme. Therefore, the following band pattern was observed in the agarose gel. A allele carriers showed a 310 bp band and the mutant G allele carrier showed both 104 and 206 bp bands.
The obtained results revealed the following:
There was a significant difference between the studied groups as regards the presence of positive family history, systemic arterial hypertension, diabetes, hypercholesterolemia, elevated level of LDL (p<0.05), but there was no significant difference between the studied groups as regards smoking, hypertriglyceridemia and low level of HDL (p >0.05), (table 10).
As regards AT2R A1675G polymorphism among the studied groups, A1675G polymorphism did not have any influence on the risk for CAD. There was no significant difference between the studied groups as regards allele frequencies (p>0.05). AT2R A allele was associated with a non-significant risk of MI versus the G allele (OR = 0.883; 95% CI = 0.332–2.349), p> 0.05 (table 11).
There was no significant relation between AT2R polymorphism and the different risk factors of CAD such as the presence of positive family history, diabetes, smoking, hyperlipidemia and arterial hypertension (table 12, 13).
However, when the population was split into hypertensive and non-hypertensive, a striking effect of the polymorphism on the risk for CAD was observed among hypertensive individuals, (OR = 3.029; 95% CI = 1.02–8.992), p < 0.05. This finding suggests that A1675G polymorphism affects CAD risk only in the presence of arterial hypertension, (table 14).
In the present study, there is no significant difference in genotypes of AT2R A1675G polymorphism when stratified against severity of CAD which was determined angiographicaly by number of vessels occluded and grade of obstruction of coronary vessels (P>0.05), (table 16).
Conclusion:
By analyzing A1675G polymorphism of the AT2R gene considering the results of this study, one can conclude that no correlation exists between that gene polymorphism, the risk of acute myocardial infarction and the severity of coronary artery disease. A1675G polymorphism affects CAD risk only in the presence of arterial hypertension. This predisposes to an imbalance between AT1R and AT2R promoting coronary atherosclerosis.
Recommendation
Several other studies on gene polymorphisms, particularly those related to the renin-angiotensin system, are needed to be carried out and may definitely establish the causal role played by these genes.