[Risk of cerebral vasospasm following subarachnoid hemorrhage is associated with endothelial nitric oxide synthase gene polymorphism].
OBJECTIVE
To study whether endothelial nitric oxide synthase gene (eNOS) polymorphisms is implicated in the development of cerebral vasospasm following subarachnoid hemorrhage.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Li
Ping
P
Department of Neurosurgery, Wuhan General Hospital, Guangzhou Military District/Clinical Medical School of Southern Medical University, Wuhan 430070, China. lp88898@yahoo.com.cn
Ma
Lian-ting
LT
Zhang
Xiao-zheng
XZ
Gong
Jie
J
Mo
Xue-hong
XH
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D020301:Vasospasm, Intracranial / Q000201:enzymology / Q000209:etiology*; D055815:Young Adult
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III