title: Gene variation in resistant hypertension: multilocus analysis of the angiotensin 1-converting enzyme, angiotensinogen, and endothelial nitric oxide synthase genes.
abstract: Resistant hypertension, a complex multifactorial hypertensive disease, is triggered by genetic and environmental factors and involves multiple physiological pathways. Single genetic variants may not reveal significant associations with resistant hypertension because their effects may be dependent on gene-gene or gene-environment interactions. We examined the interaction of angiotensin I-converting enzyme (ACE), angiotensinogen (AGT), and endothelial nitric oxide synthase (NOS3) polymorphisms with environmental factors (gender, age, body mass index, glycemia, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate, and urinary sodium excretion) in 70 resistant, 80 well-controlled hypertensive patients, and 70 normotensive controls. All subjects were genotyped for ACE insertion/deletion (rs1799752); AGT M235T (rs699), and NOS3 Glu298Asp (rs 1799983). Multifactorial associations were tested using two statistical methods: the traditional parametric method (adjusted logistic regression analysis) and gene-gene and gene-environment interactions evaluated by multifactor dimensionality reduction analyses. While adjusted logistic regression found no significant association between the studied polymorphisms and controlled or resistant hypertension, the multifactor dimensionality reduction analyses showed that carriers of the AGT 235T allele were at increased risk for resistant hypertension, especially if they were older than 50 years. The AGT 235T allele constituted an independent risk factor for resistant hypertension.
authors: Laboratory of Cardiovascular Pharmacology, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors: Juan Carlos
authors: JC
authors: Yugar-Toledo
authors: José Fernando Vilela
authors: JF
authors: Martin
authors: José Eduardo
authors: JE
authors: Krieger
authors: Alexandre C
authors: AC
authors: Pereira
authors: Caroline
authors: C
authors: Demacq
authors: Otávio Rizzi
authors: OR
authors: Coelho
authors: Eduardo
authors: E
authors: Pimenta
authors: David A
authors: DA
authors: Calhoun
authors: Heitor Moreno
authors: HM
authors: Júnior
mesh_terms: D000808:Angiotensinogen / Q000235:genetics*; D016022:Case-Control Studies; D004351:Drug Resistance / Q000235:genetics*; D004777:Environment; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D000808:Angiotensinogen; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A