(Hypertension. 1999;33:933-936.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Lack of Evidence for Association Between the Endothelial Nitric Oxide Synthase Gene and Hypertension
From the Graduate School of Human and Environmental Studies, University of Kyoto (N.K., Y.Y.); The Institute for Adult Diseases Asahi Life Foundation, Tokyo (T.S.); the Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo (H.M., H.K., Y.Y.); and the Department of Laboratory Medicine, Shimane Medical University (T.N.).
Correspondence to Norihiro Kato, MD, PhD, Graduate School of Human and Environmental Studies, University of Kyoto, Yoshida Nihonmatsu-cho Sakyo-ku, Kyoto 606, Japan. E-mail kato{at}helios.jinkan.kyoto-u.ac.jp
Abstract—Significant association
between a Glu298Asp polymorphism of the endothelial
nitric oxide synthase (eNOS) gene and essential
hypertension was recently reported in Japanese populations, with the
298Asp variant showing a higher prevalence in hypertensive patients
(10.3% to 12.0%) than in normotensive subjects (5.0% to 5.8%). In
contrast, another study demonstrated that the 298Glu variant was
significantly associated with hypertension in a Caucasian population.
We therefore undertook an extensive association study in Japanese to
resolve these contradictory claims. A total of 1165 individuals were
selected from clinic outpatients and hospital staff in a single
institution. The relevance of the Glu298Asp polymorphism to
hypertension in this population was tested in 2 ways. First, a
case-control study was conducted in 549 hypertensive and 513
normotensive subjects within the study population, with the
2 statistic used to test the significance of an
association between eNOS genotype and the
presence of hypertension. Second, an ANOVA was used to test the
significance of an association between eNOS
genotype and the level of blood pressure within the entire
population except for 167 hypertensive subjects who had been under
treatment for hypertension. No significant association was observed in
either of the statistics tested. Allele frequencies of 298Asp were
concordant across the panels: 8.4% in hypertensive subjects, 8.2% in
normotensive subjects, and 7.9% and 9.5% in 2 additional sample
populations used as reference panels. Taken together, our results do
not support the previous observation that the molecular variant of the
eNOS gene may confer principal susceptibility for
essential hypertension but rather suggest the existence of
sampling variation.
Key Words: hypertension, essential • Japanese • genetics • nitric oxide synthase
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