Abstract 160: Genetic Polymorphism C242T On The p22-phox Subunit Of NADPH Oxidase Increases The Risk For Myocardial Infarction And Modifies The Release Of P-Selectin
Background: Enzymatic production of free radicals plays a key role in atherogenesis. The p22 phox, a component of the NADH/NADPH oxidase in phagocytes and vascular smooth muscle cells, is essential for the production of reactive oxygen species. Evidence suggests that C/T polymorphism at position 242 of the p22 phox gene may affect its enzymatic activity. However, its role in the development of premature myocardial infarction (MI) as well as its ability to modify overall oxidative stress status and endothelial injury is unknown. We examined the effect of C242T polymorphism on p22 phox gene on the risk for MI, and on the variations of ox-LDL and sP-selectin.
Methods. The study population consisted of 197 patients with first event of premature MI (aged 46.90±1.1 yrs old) and 204 age- and sex- matched controls. C242T polymorphism was detected by PCR, and levels of ox-LDL and P-selectin were determined by ELISA.
Results. The prevalence of the T allele was higher in MI patients (CC/CT/TT: 65/98/34) compared to controls (CC/CT/TT: 88/95/21, p<0.05). The risk for MI was higher in TT compared to CT+CC (1.818[95%CI:1.014 −3.258] p=0.036), or compared to CC (2.192[95%CI:1.166 – 4.121] p=0.01). Carriers of the T allele (CT+TT) also had higher risk for premature MI (1.541[95%CI:1.026 −2.312] p=0.023) compared to CC. 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 associated with slightly but not significantly higher levels of ox-LDL (83.9±7.09IU/L) compared to CT+CC (79.4±2.31 IU/L, p=NS)
Conclusions. Genetic polymorphism C242T on p22 phox, is associated with the development of premature MI, since the presence of 242T allele increases the risk for MI in young individuals. Furthermore, our findings suggest that although C242T polymorphism is associated with higher levels of P-selectin, it fails to predict plasma levels of ox-LDL, suggesting that it may exert its effect at a local level inside the vessel wall and not by modifying the overall oxidative stress status.