ABSTRACT
Objective To study the effect ofT-786C polymorphism of endothelial NO synthase gene on cerebral circulation in smokers with aneurysmal subarachnoid hemorrhage. Methods Three hundred and ninety-four patients with aneurysmal subarachnoid hemorrhage were adopted in our study;smokers and nonsmokers were defined by 200 and 0, respectively, according to the smoking index (quantity of cigarettes per year). Transcranial color-coded Doppler (TCCD) was employed to detect the alterations of flow velocity of cerebral arteries. Genotyping ofT-786C was performed by using a newly developed allele-specific polymerase chain reaction. Degree of oxidative stress of these patients were evaluated by measuring the level of F2-isoprostane excretion in the urine. Results The mean flow velocity (Vm) of middle cerebral artery (MCA) and internal carotid artery (ICA) was obviously increased as compared with that of the other normal ones in most of the smokers. The Vm of MCA and ICA in nonsmokers was not obviously different as compared with the normal values. The 3 genotypes ofT-786C in smokers showed significant difference in Vm of MCA and ICA (P＜0.05); the Vm of CC genotype ([60.73±63.58] cm/s) was obviously increased as compared with that of TT ([95.8±53.5] cm/s) and TC ([93.6±51.6] cm/s) genotypes (P＜0.05). The 3 genotypes ofT-786C in nonsmokers did not show significant difference in Vm of MCA and ICA (P＞0.05). The level of F2-isoprostane excretion in smokers was significantly higher than that in nonsmokers (P＜0.05). Conclusion The T-786C polymorphism of endothelial NO synthase gene can increase cerebrovascular Vm by enhancing the cerebrovascular circulation of smokers with aneurysmal subarachnoid hemorrhage.
ABSTRACT
<p><b>OBJECTIVE</b>To study whether endothelial nitric oxide synthase gene (eNOS) polymorphisms is implicated in the development of cerebral vasospasm following subarachnoid hemorrhage.</p><p><b>METHODS</b>Three groups of patients with subarachnoid hemorrhage were selected to test this hypothesis, including 98 patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage (ASAH), 96 with cerebral vasospasm following traumatic subarachnoid hemorrhage (TSAH), and 195 patients without cerebral vasospasm following aneurysmal or traumatic subarachnoid hemorrhage. The parents of 194 patients and 100 control subjects were also examined for transmission disequilibrium test according to a family-based study design to test the associations.</p><p><b>RESULTS</b>We examined four eNOS gene polymorphisms, and two of these polymorphisms, the T to C substitution in the promoter at position -786 and the a-deletion/b-insertion in intron 4, were found to associate with cerebral vasospasm in subarachnoid hemorrhage in the case-control comparisons. For the former polymorphism, the risk of cerebral vasospasm was higher in C allele homozygotes than in the other two genotypes (odds ratio: 2.8, 95% CI: 1.4 to 5.6); for the latter polymorphism, the a-deletion carriers were exposed to a increased risk (odds ratio: 2.3, 95% CI: 1.3 to 4.0) in comparison with the noncarriers. The two polymorphisms were analyzed together as haplotypes in a family-based study using the transmission disequilibrium test. The C/a-deletion haplotype was transmitted from the heterozygous parents to cases of cerebral vasospasm in subarachnoid hemorrhage with a significantly higher frequency than expected (P=0.005).</p><p><b>CONCLUSION</b>The findings of the case-control and family-based studies clearly demonstrate that DNA sequence differences in eNOS gene influence the risk of cerebral vasospasm in subarachnoid hemorrhage.</p>
