Association of the C242T polymorphism of the p22 phox gene with advanced carotid atherosclerosis in type 2 diabetes

Reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase is an important source of superoxide (O2−) in human blood vessels. A critical component of this oxidase is the p22phox protein, which is encoded by the cytochrome b-245 α (CYBA) gene. Studies have suggested a possible association between polymorphisms of the CYBA gene and susceptibility to atherosclerosis in diabetes mellitus (DM). To address this hypothesis, we examined the relationship between the C242T polymorphism of the p22 phox gene and carotid intima/media thickness (IMT) as a factor of atherosclerosis in a group of type 2 DM patients. The study included 40 type 2 diabetic patients and 20 healthy individuals as controls. All patients and controls were matched in terms of age, gender, lipid profile, blood pressure and body mass index (BMI) The C242T p22 phox polymorphism was investigated by RFLP-PCR, and carotid IMT was measured by color duplex scanning. Diabetic subjects with the T242C and T242T genotypes displayed a significantly lower average of carotid IMT (mean 1.033±0.143 mm, range 0.85-1.25, P<0.0001) than did those with the C242C genotype (mean 1.36±0.177 mm, range 0.98-1.63) despite no differences in other risk factors. The average carotid IMT of both diabetic groups was significantly higher than that of the controls (mean 0.828±0.072 mm, range 0.72-0.86, P<0.0001). In non-diabetic subjects, the average carotid IMT of the TC+TT group did not differ from that of the CC group (0.81±0.08 vs. 0.84±0.069 mm, P>0.05). There was a significant positive correlation between carotid IMT and blood glucose level and duration. Our findings demonstrate that the CC genotype of the p22 phox gene is a risk factor for the progression of atherosclerosis in diabetic patients.