The C242T polymorphism of the NAD(P)H oxidase p22phox subunit is associated with an enhanced risk for cerebrovascular disease at a young age.
OBJECTIVE
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.


CONCLUSIONS
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.
Genius
Just
J
Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig Maximilian University, Munich, Germany. just.genius@med.uni-muenchen.de
Grau
Armin J
AJ
Lichy
Christoph
C
D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*
D019255:NADPH Oxidases; C086986:CYBA protein, human