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(Hypertension. 2003;41:355.)
© 2003 American Heart Association, Inc.

Scientific Contributions

NOS3 Genotype–Dependent Correlation Between Blood Pressure and Physical Activity

Tomomi Kimura; Tetsuji Yokoyama; Yasuhiro Matsumura; Nobuo Yoshiike; Chigusa Date; Masaaki Muramatsu; Heizo Tanaka

From the Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University (T.K., M.M.), Tokyo, Japan; the Department of Technology Assessment and Biostatistics, National Institute of Public Health (T.Y.), Saitama, Japan; the National Institute of Health and Nutrition (Y.M., N.Y., H.T.), Tokyo, Japan; and the Department of Nutrition and Food Sciences, Mukogawa Women’s University (C.D.), Hyogo, Japan.

Correspondence to Tomomi Kimura, Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10, Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. E-mail kimura.epi{at}mri.tmd.ac.jp

Endothelium-dependent vasorelaxation plays an important role in reduction of blood pressure and is mediated through release of nitric oxide (NO), which is generated by constitutively expressed endothelial nitric oxide synthase (NOS3). Exercise also augments NO release and has been recommended for primary prevention and improvement of hypertension, but individual responses are highly variable. We therefore postulated that genetic polymorphisms of NOS3 might interact with physical activity level to differentially influence blood pressure level. We genotyped 832 healthy Japanese (mean age of 54.4±8.6 years, 372 men and 460 women) for a polymorphism of NOS3 in intron 4 (ecNOS4a/b), using the polymerase chain reaction method, and scored their habitual physical activity level by using the rate of energy expenditure per resting metabolic rate through an interview according to a semiquantitative assessment method. Only in the subjects who had the rarer a allele (aa+ba type), systolic blood pressure was found to be inversely correlated with physical activity level (P for linear trend=0.0496, for interaction=0.0071). Eventually, this polymorphism was significantly associated with the prevalence of systolic hypertension only in the subjects who were in the lowest tertile of physical activity level (OR=2.4, 95% CI, 1.1 to 5.6, P for interaction=0.0474). In the present study, we found a significant interaction between the genotype and physical activity level on systolic blood pressure. These results might allow a better understanding of the mechanism to improve hypertension by exercise and to thereby reduce the risk of cardiovascular disease.

Key Words: nitric oxide synthase • polymorphism • blood pressure • exercise • genes • life style • cross-sectional study

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