The p22phox C242T gene polymorphism is associated with a reduced risk of angiographically verified coronary artery disease in a high-risk Finnish Caucasian population. The Finnish Cardiovascular Study.
BACKGROUND
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion, which may play an important role in the development of atherosclerosis and coronary artery disease (CAD). The p22phox, a component of the NADPH oxidase, is essential for the activation of this enzyme, and intensive expression of the p22phox has been reported in human atherosclerotic arteries. However, studies on the association of the C242T polymorphism in the p22phox gene with CAD have produced conflicting results, and the relation of this polymorphism with CAD is not well known in a population with acquired risk factors enhancing the NADPH-dependent superoxide production.


METHODS
As part of the Finnish Cardiovascular Study, a case-control study was conducted with 402 high-risk Finnish Caucasian patients undergoing coronary angiography. Genotyping was performed using the 5' nuclease TaqMan assay.


RESULTS
The prevalence of the T allele (TT + TC genotypes) was significantly lower among angiographically verified CAD patients (n = 250) than among control subjects (n = 152, P = .013). In contrast to subjects with the CC genotype, the T allele was found protective against CAD (odds ratio = 0.531, 95% CI 0.331-0.852, P = .009), and the results remained significant after adjustment for other significant coronary risk factors.


CONCLUSIONS
The T allele in the C242Tpolymorphism of the p22phox gene had a protective effect against the development of CAD despite the exposure of study subjects to risk factors related to excessive NADPH-dependent superoxide production.
Fan
Meng
M
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital and Tampere University Medical School, Tampere, Finland. meng.fan@uta.fi
Kähönen
Mika
M
Rontu
Riikka
R
Lehtinen
Rami
R
Viik
Jari
J
Niemi
Mari
M
Nieminen
Tuomo
T
Niemelä
Kari
K
Pörsti
Ilkka
I
Kööbi
Tiit
T
Turjanmaa
Väinö
V
Lehtimäki
Terho
T
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011859:Radiography; D012307:Risk Factors; D013481:Superoxides / Q000097:blood; D044465:White People / Q000235:genetics*
D013481:Superoxides; D019255:NADPH Oxidases; C086986:CYBA protein, human