A novel CYBA variant, the -675A/T polymorphism, is associated with essential hypertension.
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.
Moreno
María U
MU
Division of Cardiovascular Sciences, Centre for Applied Medical Research, University Clinic, University of Navarra, Pamplona, Spain.
San José
Gorka
G
Fortuño
Ana
A
Beloqui
Oscar
O
Redón
Josep
J
Chaves
Felipe J
FJ
Corella
Dolores
D
Díez
Javier
J
Zalba
Guillermo
G
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
D017931:DNA Primers; D019255:NADPH Oxidases; C086986:CYBA protein, human