A component of this enzyme is the gene, p22PHOX, which plays a critical role in the generation of reactive oxygen species (ROS). p22PHOX is found in phagocytes, vascular cells and platelets, and it contains one of the potential NADPH oxidase heme binding sites that are indispensable for enzyme activation and function. The genetic polymorphism C242T occurs in the p22PHOX gene when histidine is replaced by tyrosine at amino acid position 72.
The researchers, led by Mrs Carmen Vasiliadou (Ippokration Hospital, Athens, Greece), investigated how polymorphisms of C242T, located at the potential heme binding site, might influence MI. They identified 202 patients with premature MI (defined as under the age of 49) and 227 healthy controls. Using PCR, they detected the C242T polymorphism, and they measured ox-LDL as a key marker of oxidative stress status and P-selectin as an indirect index of platelet activation.
Results showed that in the C242T polymorphism the prevalence of the T allele was higher in MI patients than in the controls (p<0.05). The combination was CC/CT/TT: 65/98/34 in MI patients compared to CC/CT/TT: 88/95/21 in controls.
In addition, homozygosity for the T allele in the overall population was associated with higher levels of P-selectin (39.9±1.6ng/ml) compared to CT+CC (32.08±2.8ng/ml p<0.05). However, homozygosity for the T allele was not associated with significantly higher levels of ox-LDL compared to CT+CC.
Mrs Vasiliadou said the significance of finding C242T polymorphism was associated with higher levels of P-selectin, but failed to predict plasma levels of ox-LDL, might be that it exerted its effect at an intracellular level without modifying the oxidation of biological structures identifiable in the circulation.
“Once a T homozygote is identified, we can tell that this subject may have higher platelets activation state and speculate that such people might benefit from more aggressive antiplatelet therapy,” said Mrs Vasiliadou.
She said large population-based, prospective studies were needed to confirm these findings, followed by interventional studies to examine whether antiplatelet therapy had the potential to modify risks.