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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.

Renin-angiotensin and kallikrein-kinin systems are interconnected, regulating blood pressure homeostasis. We have demonstrated the interactions among polymorphisms of the angiotensinogen (AGT) and endothelial nitric oxide synthase (NOS3) genes and conventional risk factors affecting the hypertension occurrence. Individuals were recruited (n=192) and classified into hypertensive (HG; n=140) and normotensive (NG; n=52) groups. The genotypic distribution of the Met235Thr (AGT) and Glu298Asp (NOS3) polymorphisms demonstrated that both are independent risk factors of hypertension (p=0.02 and p=0.008, respectively). The concomitant presence of these polymorphisms in the HG group was significantly different (p=0.001) from the NG. Both gene polymorphisms presented an additive effect for the unfavourable alleles T and A, respectively, and 95% of the double mutant homozygotes were classified into the HG. Specific interactions among certain conventional factors and the presence of at least one unfavourable allele presented significant odds towards hypertension. Blood pressure homeostasis was affected by genetic polymorphisms conditioned by the T and A alleles of the AGT and NOS3 genes, respectively, which acted independently. However, their interaction with smoking, sedentariness, age and total cholesterol may have increased the predisposition to hypertension, which may explain most of the hypertension cases.

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...

Despite the considerable morbidity and mortality of Yellow fever virus (YFV) infections in Brazil, as well as its widespread presence in non-human primate host, our understanding of disease outbreaks is hampered by limited viral genomic data. Determining the timing and spatial corridors of YFV spread, as well as the geographic hotspots that link the endemic north of the country with epidemic extra-Amazonian regions, are central to predicting and preventing future outbreak events and epidemics. Here, we tracked the recent spread of the virus by integrating genome sequences of new YFV infections sampled from infected non-human primates and humans with both epidemiological and vector data. Through a combination of phylogenetic and epidemiological models we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modelling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centres in the Southeast. Phylodynamic analysis unravelled the circulation of three distinct YFV lineages, and provided proof of the directionality of a known spatial corridor of viral spread that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with field sampling of animals and humans within a One Health framework can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.