title: Angiotensinogen 235T allele "dosage" is associated with blood pressure phenotypes.
abstract: 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. 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. Individuals (n=1421) were randomly selected from the general population of the Vitoria City Metropolitan area. 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. No association was found between ACE variants and blood pressure phenotypes. 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). Genotypic analysis contemplating both ACE and AGT variants in the same model did not show any significant interaction between both genetic polymorphisms. 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). 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.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.forename: Glória F A
authors.initials: GF
authors.lastname: Mota
authors.forename: Roberto S
authors.initials: RS
authors.lastname: Cunha
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Herbenhoff
authors.forename: José G
authors.initials: JG
authors.lastname: Mill
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D000808:Angiotensinogen / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
chemical_list: D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A