Association between the Glu298Asp polymorphism in the endothelial constitutive nitric oxide synthase gene and brain infarction

Background and Purpose-Nitric oxide (NO) synthesized by endothelial constit utive NO synthase (ecNOS) plays a key role in vascular regulation and ather osclerosis. Little is known concerning the role of the ecNOS gene (NOS3) as a risk factor for brain infarction (BI). Our aim was to investigate the re lation between the Glu298Asp polymorphism in exon 7 of NOS3 with BI and its subtypes. Methods-Patients (n = 460; cases) with BI were consecutively recruited and classified into etiological subtypes. Control subjects (n = 460; controls) without a history of stroke were recruited among individuals hospitalized a t the same institutions and individually matched on age, sex, and center, G enotypes of the polymorphism were determined by polymerase chain reaction. Results-The distribution of genotypes was significantly different between c ases and controls (P = 0.008); the GG genotype was more frequent in cases ( 46.1%) than in controls (35.4%; OR, 1.56; 95% CI, 1.19 to 2.04). Among subt ypes, the frequency of the GG genotype was significantly higher in cases th an in controls in the lacunar subtype (OR, 2.00; 95% CI, 1.05 to 3.80); in this group, the relation between BI and LDL level was stronger among carrie rs of the GG genotype than among noncarriers (P for interaction, 0.05). Conclusions-Homozygosity for the G allele of the Glu298Asp polymorphism in NOS3 was associated with BI, and especially with lacunar stroke. Our findin gs suggest that genetic susceptibility and LDL cholesterol have a synergist ic relation. Although these findings should be replicated in a larger sampl e of subjects and the functionality of the Glu298Asp polymorphism has not b een established, these results may help us to understand the cause of the a rteriolopathy underlying lacunae and have future implications in their trea tment and prevention.