Association of endothelial nitric oxide synthase polymorphism G894T with functional outcome in acute stroke patients

Endothelial nitric oxide synthase (eNOS) G894T polymorphism has been previously associated with vascular diseases including stroke, but often with conflicting results. Experimental evidence suggests that some eNOS modalities may be important in preventing stroke, while others may be important during the dynamic inflammatory processes triggered at the acute phase of stroke. Thus, we examined the possible association of eNOS G894T variation with stroke severity and functional outcome.

One hundred and eight consecutive patients with first ever acute atherothrombotic or lacunar stroke, and 193 stroke-free subjects were recruited. Demographic data, medical history, and vascular risk factors were collected. Assessments for stroke severity and functional outcome were carried out on admission and at one month post-stroke, respectively. eNOS G894T genotypes were produced using a standard restriction-fragment-length polymorphism technique.

eNOS G894T polymorphism genotypic distributions did not differ between stroke patients and controls, as well as between each stroke subtype and controls. Carriage of T allele (GT and TT genotypes versus GG) was not significantly associated with either stroke severity or functional outcome in the univariate analysis. However, after accounting for age, gender and stroke severity, the presence of T allele strongly predicted poor outcome [odd ratio 8·49 (95% confidence intervals 1·57-46·0)]. Further adjustments for other important confounders could not alter the above significant association.

Carriers of the eNOS 894T allele are at increased risk for adverse outcome at one month post-stroke, independently of severity and other confounding factors. Therapeutic interventions targeting patients with this unfavorable mutation may be an appealing approach.