A novel CYBA variant, the -675A/T polymorphism, is associated with essential hypertension
María U. Moreno (a), Gorka San José (a), Ana Fortuño (a), Oscar Beloqui (b), Josep Redón (c), Felipe J. Chaves (c), Dolores Corella (d), Javier Díez (a,e) and Guillermo Zalba (a)
(a) Division of Cardiovascular Sciences, Centre for Applied Medical Research
(b) Department of Internal Medicine, University Clinic, University of Navarra, Pamplona
(c) Hypertension Clinic, Department of Internal Medicine, Hospital Clínico
(d) Department of Preventive Medicine, University of Valencia
(e) Department of Cardiology and Cardiovascular Surgery, University Clinic, University of Navarra, Pamplona, Spain
Revista: Journal of Hypertension
Fecha: 25/08/2007Cardiología Unidad de Chequeos
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.
A case-control study in a random sample of the general population.
CYBA polymorphisms were determined by restriction fragment length polymorphism and allelic discrimination. NADPH oxidase activity was quantified in phagocytic cells by chemiluminescence.
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.
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.
CITA DEL ARTÍCULO J Hypertens. 2007 Aug;25(8):1620-6
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