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Background The p22phox is a critical component of the superoxide-generating vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.Several polymorphisms in p22phox gene are studied for their association with cardiovascular diseases.However,no publication is available to assess the relation of 549C＞T polymorphism in p22phox gene to coronary artery disease (CAD) risk.This study was to investigate the effect of the p22phox gene 549C＞T polymorphism on CAD risk.Methods Hospital-based case-control study was conducted with 297 CAD patients and 343 healthy persons as the control group.Polymerase chain reaction and pyrosequencing using PSQ 96 MA Pyrosequencer (Biotage AB) were used to detect the polymorphisms.Multiple Logistic regression model was used to adjust the potential confounders and to estimate odds ratio (OR) with 95％ confidence intervals (Cls).Results The observed genotype frequencies of this polymorphism obeyed the Hardy-Weinberg equilibrium in both cases (P=0.439) and controls (P=0.668).The frequency of mutant genotypes (TT+CT) in cases (41.08％) was higher than that in controls (36.73％) with an OR=-1.20 (95％ CI=0.87-1.65).After the adjustment of the potential confounders,there was a significant association of the mutant genotypes with increased risk of CAD (OR=1.57,95％ CI=1.01-2.46,P=0.047).Conclusions The mutant genotypes of the p22phox gene 549C＞T polymorphism had a significant effect on the increased risk of CAD in this studied population.