title: Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation, but not to resistance to antihypertensive drug therapy.
abstract: OBJECTIVE
  Most hypertensive patients require two or more drugs to control arterial blood pressure effectively. Although endothelial nitric oxide synthase (eNOS) haplotypes have been associated with hypertension, it is unknown whether eNOS genotypes/haplotypes are associated with resistance to antihypertensive therapy.
  
  
  METHODS
  We studied the distribution of three eNOS genetic polymorphisms: single nucleotide polymorphisms in the promoter region (T(-786)C), and in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (b/a). Genotypes were determined for 111 normotensive controls (NT), 116 hypertensive individuals who were well controlled (HT), and 100 hypertensive individuals who were resistant to conventional antihypertensive therapy (RHT). We also compared the distribution of eNOS haplotypes in the three groups of subjects.
  
  
  RESULTS
  No differences were found in genotype or allele distribution among the three groups (all P > 0.05). Conversely, the 'C Glu b' haplotype was more commonly found in the NT than in the HT or RHT groups (21 versus 8 and 7%, respectively; both P < 0.00625). In addition, the 'C Asp b' haplotype was more commonly found in the HT or RHT groups than in the NT group (22 and 20%, respectively, versus 8%; both P < 0.00625). The distribution of eNOS haplotypes was not significantly different in the HT and RHT groups (P > 0.05).
  
  
  CONCLUSIONS
  Whereas our findings suggest a protective effect for the 'C Glu b' haplotype against hypertension and that the 'C Asp b' haplotype increases the susceptibility to hypertension, our results suggest that eNOS haplotypes are not associated with resistance to antihypertensive therapy.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Valéria C
authors.initials: VC
authors.lastname: Sandrim
authors.forename: Juan C
authors.initials: JC
authors.lastname: Yugar-Toledo
authors.forename: Zeruesenay
authors.initials: Z
authors.lastname: Desta
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D004351:Drug Resistance / Q000235:genetics* / Q000502:physiology; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D052250:Nitric Oxide Synthase Type III