Human Genetics

, Volume 103, Issue 1, pp 65–69

A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese

Authors

  • Michihiro Yoshimura
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • H. Yasue
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • Masafumi Nakayama
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • Yukio Shimasaki
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • Hitoshi Sumida
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • Seigo Sugiyama
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • Kiyotaka Kugiyama
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • Hisao Ogawa
    • Division of Cardiology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860–8556, Japan e-mail: yasue@kumamoto-u.ac.jp, Tel.: +81 96 373 5175, Fax: +81 96 362 3256
  • Yoshihiro Ogawa
    • Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8397, Japan
  • Yoshihiko Saito
    • Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8397, Japan
  • Yoshihiro Miyamoto
    • Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8397, Japan
  • Kazuwa Nakao
    • Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8397, Japan
Original Investigation

DOI: 10.1007/s004390050785

Cite this article as:
Yoshimura, M., Yasue, H., Nakayama, M. et al. Hum Genet (1998) 103: 65. doi:10.1007/s004390050785

Abstract

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise from interactions between environmental and genetic factors. Endothelial derived nitric oxide (NO) has been implicated in the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire 26 coding regions. The variant is significantly associated with coronary spasm.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998