Genetic polymorphisms G894T on the eNOS gene is associated with endothelial function and vWF levels in premature myocardial infarction survivors.
BACKGROUND
Genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS) gene has been associated with endothelial dysfunction in young smokers, but its role in the pathogenesis of MI is obscure. We examined the effect of G894T polymorphism on endothelial function, on markers of endothelial cells injury and activation such as von Willebrand factor (vWF) and on serum levels of proinflammatory cytokines such as interleukins 6 (IL-6) and 1b (IL-1b), in young myocardial infarction (MI) survivors.


METHODS
The study population consisted of 56 patients with a history of premature MI. The forearm blood flow (FBF) was measured by using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin. G894T polymorphism was determined by polymerase chain reaction (PCR), while plasma vWF and serum IL1b and IL-6 levels were determined with ELISA.


RESULTS
There was no significant difference in resting FBF and in the responses to nitroglycerin between the genotypes. However, the presence of T allele (GT+TT, n=35) was associated with decreased FBF during reactive hyperemia (10.23+/-0.70 ml/100ml tissue/min) and decreased forearm vasodilatory response to reactive hyperemia (54.28+/-4.81%) compared to GG (13.82+/-0.92 ml/100 ml tissue/min and 83.92+/-9.89% respectively, p<0.01 for both). Carriers of the T allele had also higher levels of vWF (79.66+/-5.56%) compared to GG (60.94+/-5.27% p<0.05). However, no significant difference was observed in IL-1b and IL-6 serum levels between the genotypes (p=ns for both).


CONCLUSIONS
The presence of 894T allele on eNOS gene is associated with impaired endothelial function and higher levels of von Willebrand factor in relatively young patients with myocardial infarction. This finding implies that genetic polymorphism G894T on eNOS may affect endothelial function in patients with a history of premature myocardial infarction.
Antoniades
Charalambos
C
Athens University Medical School, A' Cardiology Department, Hippokration Hospital, S. Karagiorga street 69, 166 75, Glifada, Athens, Greece.
Tousoulis
Dimitris
D
Vasiliadou
Carmen
C
Pitsavos
Christos
C
Toutouza
Marina
M
Tentolouris
Costas
C
Marinou
Kyriakoula
K
Stefanadis
Christodoulos
C
D000483:Alleles; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D011110:Polymorphism, Genetic; D017741:Survivors; D014841:von Willebrand Factor / Q000235:genetics*
D014841:von Willebrand Factor; D019001:Nitric Oxide Synthase