Abstract

Genetic factors appear to be important in the pathogenesis of cerebrovascular disease. It has been reported that endothelial nitric oxide may mediate cerebral vasodilatory responses and cerebral autoregulation. Impaired cerebral autoregulation has been reported in hypertensive patients, and may predispose them toward stroke. It has been reported that the presence of the GG genotype of the nitric oxide synthase (NOs) gene is a risk factor for stroke in both normotensive and hypertensive populations. Likewise, the presence of cerebral white matter lesions (WML) also represents an early marker of cerebrovascular disease. The aim of the present study was to evaluate the possible association between the GG genotype of the NOs gene and the presence of silent cerebral WML in asymptomatic middle-aged essential hypertensive patients. Forty-nine never treated essential hypertensive patients (29 men, 20 women), aged 50-60 years (mean age 54.3 ± 4.2 years) without clinical evidence of target organ damage were studied. Patients with diabetes mellitus, carotid stenosis >50% or daily alcohol intake >30g were excluded. All patients underwent 24-hour ambulatory blood pressure monitoring and brain-magnetic resonance imaging in order to establish the presence or absence of cerebral white matter lesions, using the Rotterdam scale. All patients were also genotyped by polymerase chain reaction for the polymorphism of the NOs gene located in exon 7 (G894T). The distribution of genotypes in the whole group of essential hypertensive patients studied was GG: 17 (34.7%), GT: 29 (59.2%), and TT: 3 (6.1%). These frequencies did not deviate from Hardy-Weinberg equilibrium. There were no significant differences in the frequency of the GG genotype between hypertensives with and without WML (36.4% versus 33.3%; P=0.907), or in G allele frequency (66% versus 63%; P=0.834). Age, gender distribution, body mass index, cholesterol and smoking habit did not differ among hypertensives classified by NOs genotype. Our results show no evidence that the presence of the GG genotype and/or the G allele of the nitric oxide synthase gene is associated with the development of cerebral white matter lesions in essential hypertensive patients.