title: Inducible nitric oxide synthase haplotype associated with hypertension and responsiveness to antihypertensive drug therapy.
abstract: Hypertension is a multifactorial disorder associated with increased inducible nitric oxide synthase (iNOS) expression and activity. While genetic polymorphisms affect iNOS expression, it is not known whether iNOS gene polymorphisms affect the susceptibility to hypertension and the responses to antihypertensive therapy. This study aimed at assessing whether iNOS polymorphisms ((CCTTT)(n), g.-1026C>A, and g.2087G>A) and haplotypes are associated with hypertension and with responsiveness to drug therapy. We studied 115 well controlled hypertensive patients (HTN), 82 hypertensive patients resistant to optimized antihypertensive therapy (RHTN), and 113 normotensive healthy subjects (NT). Genotypings were carried out using real-time polymerase chain reaction (PCR) and PCR amplification followed by capillary electrophoresis. The software PHASE 2.1 was used to estimate the haplotype frequencies in each group. Variant genotypes (GA+AA) for the g.2087G>A polymorphism were more commonly found in hypertensive patients (HTN+RHTN) than in normotensives (P=0.016; OR=2.05). We found no associations between genotypes and responsiveness to therapy (P>0.05). The S-C-A haplotype was more commonly found in hypertensive patients (HTN+RHTN) than in normotensives (P=0.014; OR=6.07). Interestingly, this haplotype was more commonly found in the HTN group than in the RHTN group (P=0.012; OR=0.14). Our findings indicate that the g.2087G>A polymorphism in the iNOS gene affects the susceptibility to hypertension. Moreover, while the S-C-A haplotype is associated with hypertension, it is also associated with responsiveness to antihypertensive therapy.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Oliveira-Paula
authors.forename: Riccardo
authors.initials: R
authors.lastname: Lacchini
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Coeli-Lacchini
authors.forename: Heitor Moreno
authors.initials: HM
authors.lastname: Junior
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001499:Bayes Theorem; D016022:Case-Control Studies; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D015999:Multivariate Analysis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D000959:Antihypertensive Agents; D052247:Nitric Oxide Synthase Type II