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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:605.)
© 2002 American Heart Association, Inc.

Vascular Biology

T-786C Polymorphism in Endothelial NO Synthase Gene Affects Cerebral Circulation in Smokers

Possible Gene-Environmental Interaction

Shampa Nasreen; Toru Nabika; Hiroshi Shibata; Hidehiko Moriyama; Kazuya Yamashita; Junichi Masuda; Shotai Kobayashi

From the Department of Laboratory Medicine (S.N., T.N., J.M.), Central Clinical Laboratory (H.S., H.M.), and the Third Department of Internal Medicine (K.Y., S.K.), Shimane Medical University, and the Shimane Institute of Health Science (T.N., K.Y., S.K.), Izumo, Japan.

Correspondence to Toru Nabika, MD, Department of Laboratory Medicine, Shimane Medical University, Izumo 693, Japan. E-mail nabika{at}shimane-med.ac.jp

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 200 and 0, respectively. One hundred sixty-six male nonsmokers and 344 male smokers were recruited. Cerebral blood flow was measured by the ¹³³Xe inhalation method. Genotyping of T-786C was performed by using a newly developed allele-specific polymerase chain reaction. Smokers were exposed to greater oxidative stress, as estimated by urinary F₂-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.

Key Words: nitric oxide synthase • polymorphism • cross-sectional studies • cerebral circulation

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