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

Michihiro Yoshimura, Hirofumi Yasue, Masafumi Nakayama, Yukio Shimasaki, Hitoshi Sumida, Seigo Sugiyama, Kiyotaka Kugiyama, Hisao Ogawa, Yoshihiro Ogawa, Yoshihiko Saito, Yoshihiro Miyamoto, Kazuwa Nakao

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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.

Original languageEnglish
Pages (from-to)65-69
Number of pages5
JournalHuman Genetics
Volume103
Issue number1
DOIs
Publication statusPublished - Sep 8 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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    Yoshimura, M., Yasue, H., Nakayama, M., Shimasaki, Y., Sumida, H., Sugiyama, S., Kugiyama, K., Ogawa, H., Ogawa, Y., Saito, Y., Miyamoto, Y., & Nakao, K. (1998). A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. Human Genetics, 103(1), 65-69. https://doi.org/10.1007/s004390050785