T-786C polymorphism in endothelial NO synthase gene affects cerebral circulation in smokers - Possible gene-environmental interaction

Effects of smoking on white matter lesions, such as lacunar infarction and leukoaraiosis, are still controversial. We hypothesized that the endothelial NO synthase (eNOS) genotype was a modulating factor for the effect of smoking on cerebral circulation. We took a cross-sectional population from the participants of a health examination to study the effects of smoking and a single-nucleotide polymorphism in the eNOS gene, T-786C. Smokers and nonsmokers were defined as having a smoking index (cigarettes per day times years) of greater than or equal to200 and 0, respectively. One hundred sixty-six male nonsmokers and 344 male smokers were recruited. Cerebral blood flow was measured by the Xe-133 inhalation method. Genotyping of T-786C was per-formed by using a newly developed allele-specific polymerase chain reaction. Smokers were exposed to greater oxidative stress, as estimated by urinary F-isoprostane excretion. In smokers, CC homozygotes of T-786C showed a significant decrease of cerebral blood flow (56.6 +/- 13.3, 57.6 +/- 11.5, and 44.0 +/- 7.2 mL/min per 100 g tissue for TT, TC, and CC, respectively; P=0.03 by ANOVA) and a significant increase of cerebrovascular resistance, whereas the eNOS genotype did not affect these parameters in nonsmokers. This result indicated that the eNOS genotype could modify cerebrovascular circulation in a general population by potentiating the adverse effect of smoking.