The C242T polymorphism of the NAD(P)H oxidase p22(phox) subunit is associated with an enhanced risk for cerebrovascular disease at a young age

Background and Purpose: Oxidative stress has been proposed as a
major contributing factor for vascular disease, that acts
independently from its participation in predisposing disorders such
as diabetes and arterial hypertension. A functionally relevant
C242T polymorphism of the CYBA gene encoding the NAD(P)H oxidase
p22(phox) subunit, is supposed to lead to an abnormal reduction in
the generation of reactive oxygen species in vascular smooth-muscle
and endothelial cells. Methods: We investigated the p22(phox) C242T
single-nucleotide polymorphism by polymerase chain reaction in
consecutive patients with ischemic stroke or transient ischemic
attack under the age of 50 (n = 161) and in population-based
control subjects (n = 136). Results: Homozygosity for the T variant
was associated with an enhanced risk for cerebral ischemia (odds
ratio 3.85, confidence interval 1.39-10.64) after adjusting for
classical risk factors. Risk for cerebral ischemia was not
increased in heterozygous subjects. Conclusion: The p22(phox) C242T
single-nucleotide polymorphism is associated with stroke risk. This
finding supports the hypothesis that oxidative stress may
contribute to stroke pathogenesis. Copyright (C) 2008 S. Karger AG,
Basel.