C242T polymorphism of NADPH oxidase p22phox and recurrence of cardiovascular events in coronary artery disease.
OBJECTIVE
The common C242T polymorphism in the gene for the p22phox subunit of NADPH oxidase has been reported to be negatively associated with oxidative stress, but whether it confers prognostic information is not yet clear.


RESULTS
The incidence of major adverse cardiovascular events (MACE) were determined in 237 patients with coronary stenosis during a median follow-up of 7.8 years. The p22phox genotypes were evaluated in 213 patients (89.9%) by polymerase chain reaction and RsaI. digestion. Plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, were also measured. In the univariate analysis, patients with CT/TT genotypes showed reduced recurrence of cardiovascular deaths, nonfatal MI, and revascularization procedures compared with homozygous carriers of the C allele. After controlling for confounders, a significantly lower risk of new revascularization procedures (HR=0.31, 95% CI 0.12 to 0.70; P=0.014) remained associated with the T allele. The Kaplan-Meier analysis showed a longer survival free from fatal and nonfatal MI in carriers of T allele (P<0.001). The presence of the 242T allele was associated with significantly reduced plasma concentrations of 8-OHdG.


CONCLUSIONS
The 242T allele was a predictor of lower risk of recurrence of cardiovascular events in high-risk patients and was associated with reduced systemic oxidative stress.
Arca
Marcello
M
Department of Clinical and Medical Therapy, Unit of Medical Therapy, La Sapienza University, Rome, Italy.
Conti
Beatrice
B
Montali
Anna
A
Pignatelli
Pasquale
P
Campagna
Filomena
F
Barillà
Francesco
F
Tanzilli
Gaetano
G
Verna
Roberto
R
Vestri
Annarita
A
Gaudio
Carlo
C
Violi
Francesco
F
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors
D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019255:NADPH Oxidases; C086986:CYBA protein, human; D003849:Deoxyguanosine