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No association was found between the angiotensinogen gene M235T polymorphism and coronary artery disease, neither with its severity nor with acute myocardial infarction.

ObjectiveTo assess the association of the A1166C polymorphism of the angiotensin II type-1 receptor (AT1R) gene with acute myocardial infarction and also with the severity of coronary artery disease. (OR = 1.35; AC vs AA (OR = 1.03; and AA+AC vs AA (OR = 1.33;. None of the severity criteria showed a significant correlation with the genotypes. Methods Conclusion According to our results, no correlation exists between the A1166C polymorphism of the angiotensin II type-1 receptor (AT1R) gene and acute myocardial infarction or the severity of coronary artery disease. Key words A1166C polymorphism, angiotensin II, acute myocardial infarction, coronary artery diseaseThe renin-angiotensin system comprises a cascade of enzymatic reactions, which results in the production of angiotensin II from the angiotensinogen substrate. The physiological effects of angiotensin II are mediated by a final common pathway, through angiotensin II binding to specific receptors located on the cell membrane 1,2 . Two isoforms of endothelial receptors for angiotensin II are known so far: AT1 and AT2. Most of their physiological effects are mediated by the activation of AT1-subtype receptors. The receptors belong to the superfamily of the G-protein-coupled receptors, and, in the case of AT1 receptors (AT1R), coupling occurs via Gq proteins. Consequently, stimulation of AT1 receptors activates phospholipase C, increases the levels of diacylglycerol (DAG) and inosotol triphosphate (IP3), elevates the intracellular Ca +2 concentration, and activates several kinases, modulating cell functions 3,4 . Angiotensin II acts as a mitogen in vascular smooth muscle cells by activating several signaling pathways, such as that of phospholipase C, phospholipase A 2 , and phospholipase D, as well as by activating a large number of kinases, such as tyrosine kinases, mitogen-activated protein kinases (MAPKs), c-src kinase, Janus-associated tyrosine kinase, and receptors with tyrosine-kinase activity. Angiotensin II also stimulates transcription factors, such as the activating protein 1, signal transduction and transcription activators (STATs), and the nuclear factor kappa B (NFkB) 5,6 . Several studies have reported that the proliferative effects of angiotensin II are mediated by the activation of AT1 receptors 7 . More recently, a study including patients with myocardial infarction and high circulating levels of angiotensin II reported that the administration of AT1R antagonists had a significant pharmacotherapeutic implication 8 . Cloning of cDNA of the AT1 receptor provided the identification of a polymorphism in the nontranslated region 3' (A1166C), corresponding to an A→C transversion (adenine replaced by cytosine) in the position of the nucleotide 1166 of the mRNA sequence, resulting in 1 heterozygous (AC) and 2 homozygous (CC and AA) genotypes 9 . The homozygous CC genotype seems to be associated with a greater incidence of myocardial infarction 10 . Increasing evidence has shown the importance of the participation of the renin-angiotensin system in th...