Abstract 3693: Genetic Variability Of Nitric Oxide Synthase And The Risk For Myocardial Infarction: Evidence For Interactions With Inflammatory Response And Endothelial Injury During The Acute Phase Of Myocardial Infarction
Background: Genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS) has been associated with increased cardiovascular risk. However its role during the acute phase of myocardial infarction (MI) is unknown. We evaluated the effect of G894T polymorphism on the risk for premature MI and on the release of von Willebrand factor (vWF), interleukin-6 (IL-6) and oxidized LDL levels (ox-LDL) during the acute phase of premature MI and one year after the event.
Methods. The study population consisted of 228 patients with first event of premature MI (aged 46.96±0.4 yrs old) and 519 age- and sex- matched controls. One year after the event, 61 patients and 205 controls were recalled for the follow-up study. Blood samples were taken from patients during the acute phase of MI and after 1 year. G894T polymorphism was detected by PCR, and levels of vWF, IL-6 and ox-LDL were determined by ELISA.
Results. The frequencies of GG, GT and TT were 97 (42.5%), 99(43.5%) and 32 (14%) in MI and 255(49.1%), 217(41.8%) and 47 (9.1%) in controls. The risk for MI in TT was 1.840 (95%CI: 1.078 to 3.142) p<0.05 compared to GG+GT and 2.01(95%CI:1.118 to 3.606) p<0.05 compared to GG. Carriers of the T allele had higher vWF levels during the acute phase of MI (121.02±5.47%) compared to GG (84.6±7.1%, p<0.01), an effect that persisted after 1 year (90.4±3.8 vs 73.1±4.6%, p<0.01), while there was no difference between carriers of the T-allele and GG in controls (74.3±3.0% vs 77.5±3.2%). During the acute phase of MI, carriers of the T allele had higher ox-LDL and IL-6 (131.2±6.4 ng/ml and 8.5±0.7pg/ml respectively) compared to GG (101.7± 9.64 ng/ml and 6.2± 0.8 pg/ml, p<0.05 for both), but there was no difference at one year (98.9±6.8 ng/ml and 3.7±0.43 pg/ml vs 84.6±6.7ng/ml and 3.1±0.3 pg/ml respectively, p=NS for both). No difference was observed in ox-LDL or IL-6 levels between carriers of the T allele (72.4±2.7 ng/ml and 2.07±0.2 pg/ml) and GG (70.4±2.6 ng/ml and 2.27±0.23 pg/ml respectively, p=NS for both) among healthy individuals.
Conclusions. The G894T polymorphism on eNOS gene increases the risk for premature MI, and modifies the response of vascular endothelium during the acute phase of MI by affecting the release of vWF, IL-6 and oxidative stress status, an effect diminished one year after the event.