الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 168 |  |  |
| | | from | 168 | | |
Abstract
The Renin-angiotensin system (RAS) plays an important role in blood pressure regulation & homeostasis and it is involved in pathogenesis of coronary artery disease & myocardial infarction. Circulating Renin catalyzes the Angiotensinogen (AGT) to Ag I conversion. The AGT gene is expressed in the liver, the site of AGT synthesis and release into the circulation. RAS functions as a paracrine system. Angiotensin-II is demonstrated to be produced in multiple target organs by local RAS pathways components which are found in the walls of blood vessels, in the uterus, the placenta, and the fetal membranes.
Many polymorphisms in the Angiotensinogen gene have been discovered. Several studies have evaluated the relative risk of cardiovascular diseases conferred by gene variants of the Renin-angiotensin system. Reported in the ”Etude Cas-Témoin de l’Infarctus du Myocarde” (ECTIM) an association between variants of the ACE gene and myocardial infarction in Caucasian patients considered at little risk of cardiovascular diseases according to their lipid profile and body mass index. The same case and control populations (630 patients who survived a myocardial infarction and 741 controls) were used to explore the role of the M235T and T174M AGT gene variants in the pathogenesis of coronary disease. Although they found no difference in the AGT genotype distributions in the cases and controls, carriers of the M174 allele were more often receiving antihypertensive treatment, and a greater proportion of them required several drugs. Three other studies have shown an association between the M235T AGT allele and coronary heart disease.
A single nucleotide polymorphism (SNP) in the 3-prime untranslated region (3′ UTR) of this gene (A1166C, rs5186) has been characterized and investigated in relation to essential hypertension, left ventricular hypertrophy, MI, carotid inti-medial thickening and stroke in a limited number of populations.
In relation to the association of AT1R/A1166C polymorphism with diabetes, a recent study has indicated that the risk of developing diabetes in subjects who are under treatment with angiotensin II receptor blockers is 5 times higher in those with the CC genotype compared to the carriers of an allele.
This study was designed to evaluate the correlation between genetic polymorphism of AGT & AgIIR1 and CAD in type II diabetics. In which there were two groups: Group Iincluding 40 patients with type II DM & established CAD from those attending cardiology outpatient clinics of Benha university hospital from January 2010 to July 2010& group twoIncluding 19 healthy volunteers divided into 9 males & 10 females proved to be free from any heart diseases or diabetes mellitus.Among the study participants, 38 participants (64.4%) had mutant AGT M235T gene, while the other 21 participants (35.6%) had wild type gene. The prevalence of mutant gene showed non-significant difference between patients (65%) and controls (63.2%). Homozygote gene type (TT) was significantly (p<0.05) frequent in patients compared to controls.
Among the study participants, 33 participants (55.9%) had mutant AgIIR1 A1166C gene, while the other 26 participants (44.1%) had wild type gene. The prevalence of mutant gene showed non-significant difference between patients (57.5%) and controls (52.6%). Homozygote gene type (CC) was also non-significantly (p>0.05) frequent in patients compared to controls.
These data indicated an association between the presence of mutant AGT M235T gene with increased prevalence of T genotype and increased severity of CAD and multiplicity of stenosed vessels. In support of this assumption, there was a positive significant correlation between the presence of AGT M235T mutation, irrespective of homogenecity, (r=0.455, p=0.003) with the presence of more than one stenosed coronary vessel.
Despite the positive significant correlation between the presence of A1166C gene polymorphism and presence of more than one coronary vessel stenosed; regression analysis defined A1166C gene polymorphism as a significant predictor for the presence of more than one stenosed coronary vessel in the general model and disappeared in the other models. This finding indicates a fact that A1166C polymorphism per se could not predict or underlay the pathogenesis and/or presence of vascular disease, but if augmented by other predisposing factors could do.