part d assigning genotypes for codominant alleles

The insertion/deletion (I/D) ACE gene polymorphism 2 has been shown to predict approximately half of the interindividual variability in the serum 2,3 and tissue 4 levels of ACE. Two allelic variants in RAS components have been undoubtedly associated with particular intermediate phenotypes that could help explain some of the pathophysiological derangement observed in cardiovascular homeostasis. The renin-angiotensin system (RAS) plays a key role in the maintenance of cardiovascular homeostasis. In this scenario, the study of components of important physiological control systems known to contribute to the regulation of blood pressure can offer a unique opportunity to evaluate potential genetic mechanisms or pathways underlying interindividual blood pressure variation among humans. 1 The genetic pathways underlying this complex disease remain largely elusive because late age of onset, polygenic inheritance, genetic heterogeneity, incomplete penetrance, unknown mode of action of disease alleles, quantitative variability of blood pressure phenotypes, ethnicity, age, gender, and environmental factors, such as diet, physical activity, or smoking status, are confounding variables that may interfere in this process in an unknown fashion. The interplay between environmental and genetic factors is a major determinant of the final phenotype in hypertension. Taken together, these data indicate a linear relation between AGT 235T allele number (“dosage”) and blood pressure in an ethnically mixed urban population and confirmed its role as an independent risk factor for hypertension for men and women when in homozygosity. In addition, the AGT 235T allele was significantly associated with hypertension in a recessive model, which remained as an independent risk factor for hypertension even after adjustment for age, gender, and ethnicity (OR, 1.33 95% CI, 1.04 to 1.70). Genotypic analysis contemplating both ACE and AGT variants in the same model did not show any significant interaction between both genetic polymorphisms. However, a statistically significant association was revealed between the AGT 235T variant and all blood pressure phenotypes, consistent with an additive/codominant mode of action even after adjustment for age and gender ( P<0.01). No association was found between ACE variants and blood pressure phenotypes. Neither gender, age, smoking status, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, or diabetes was associated with ACE or AGT polymorphism in univariate analysis. Individuals (n=1421) were randomly selected from the general population of the Vitoria City Metropolitan area. In this study, we investigated the association of specific functional gene variants of the renin-angiotensin system, ACE (I/D) and angiotensinogen (M/T) genes, with blood pressure phenotypes (systolic, mean, diastolic, and pulse pressure), in an ethnically mixed urban population in Brazil. The genetic mechanisms underlying interindividual blood pressure variation among humans may reflect, at least in part, clustering of functional gene variants belonging to complex blood pressure control systems. Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).

Part d assigning genotypes for codominant alleles