title: A novel CYBA variant, the -675A/T polymorphism, is associated with essential hypertension.
abstract: OBJECTIVE
  Oxidative stress is implicated in hypertension and the NADPH oxidase systems constitute the main source of superoxide in vascular wall. We searched for new polymorphisms within the CYBA promoter, the human gene that encodes the p22phox protein, and studied their potential association with essential hypertension.
  
  
  METHODS
  A case-control study in a random sample of the general population.
  
  
  METHODS
  CYBA polymorphisms were determined by restriction fragment length polymorphism and allelic discrimination. NADPH oxidase activity was quantified in phagocytic cells by chemiluminescence.
  
  
  RESULTS
  We identified three novel polymorphisms, at positions -852, -675 and -536 from the ATG codon. Only the -675(A/T) polymorphism associated with essential hypertension. The prevalence of the TT genotype and the T allele frequency were significantly higher (P < 0.05) in hypertensives than in normotensives. Furthermore, TT hypertensives exhibited higher (P < 0.05) systolic blood pressure values than TA/AA hypertensives. Increased phagocytic NADPH oxidase activity was observed in TT subjects compared to TA and AA individuals (P < 0.05). Enhanced carotid intima-media thickness, a surrogate marker of atherosclerosis, was found in TT subjects compared to TA and AA individuals (P < 0.05). Finally, mutagenesis experiments demonstrated a functional role of this polymorphism on the CYBA promoter activity.
  
  
  CONCLUSIONS
  The -675 (A/T) CYBA polymorphism may be a novel genetic marker associated with essential hypertension. Furthermore, TT subjects exhibit features of NADPH oxidase-mediated oxidative stress and asymptomatic atherosclerosis.
authors.affiliation: Division of Cardiovascular Sciences, Centre for Applied Medical Research, University Clinic, University of Navarra, Pamplona, Spain.
authors.forename: María U
authors.initials: MU
authors.lastname: Moreno
authors.forename: Gorka
authors.initials: G
authors.lastname: San José
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuño
authors.forename: Oscar
authors.initials: O
authors.lastname: Beloqui
authors.forename: Josep
authors.initials: J
authors.lastname: Redón
authors.forename: Felipe J
authors.initials: FJ
authors.lastname: Chaves
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
authors.forename: Guillermo
authors.initials: G
authors.lastname: Zalba
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015810:Linkage Disequilibrium; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D010586:Phagocytes / Q000201:enzymology; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D017931:DNA Primers; D019255:NADPH Oxidases; C086986:CYBA protein, human