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February 12, 2026Journal of Investigative Medicine

Genetic Risk Factors for Coronary Artery Spasm: Significance of Endothelial Nitric Oxide Synthase Gene T −786 →C and Missense Glu298Asp Variants

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Key result

eNOS T-786->C mutation linked to greater coronary spasm risk than smoking or hypertension.

Why the study?

Genetic linkage among three eNOS gene polymorphisms was unknown, and it was unclear which variant is most responsible for coronary spasm.

Do eNOS gene polymorphisms (T-786->C and Glu298Asp) independently predict the risk of coronary artery spasm?

Population

423 randomly selected DNA samples plus 201 patients with coronary spasm and 345 volunteers

Comparison

eNOS gene variants and conventional risk factors evaluated across patients and volunteers

Design

Case-control genetic association study

Authors

MYMichihiro YoshimuraHYHirofumi YasueGeneral CardiologyMNMasafumi Nakayama

Discussion

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Implication

May support eNOS genotyping in spasm risk assessment; extends prior associations but leaves open prospective validation.

Key Points

  • To examine genetic linkages among eNOS gene polymorphisms and their association with coronary spasm risk.
  • Assessed genotype and allele frequencies for the T −786 →C, intron 4b/a, and Glu298Asp variants in 423 DNA samples.
  • Analyzed predictive capacities of genetic and conventional risk factors using multiple logistic regression in 201 coronary spasm cases and 345 volunteers.
  • Studied the correlation between the eNOS gene polymorphisms and their influence on coronary spasm.
  • Significant linkage found between eNOS intron 4a allele and the T −786 →C mutation (P<0.00001).
  • No significant linkage between intron 4a and Glu298Asp (P=0.1437) or between Glu298Asp and T −786 →C (P=0.1996).
  • T −786 →C mutation identified as the most predictive risk factor for coronary spasm (P<0.001), followed by smoking (P<0.001), hypertension (P=0.004), and Glu298Asp (P=0.028).

Structured PICO

Do eNOS gene polymorphisms (T-786->C and Glu298Asp) independently predict the risk of coronary artery spasm?

P
Population
201 patients with coronary spasm and 345 volunteers; additionally 423 randomly selected DNA samples for genetic linkage analysis
I
Intervention
Presence of endothelial nitric oxide synthase (eNOS) gene polymorphisms (T-786->C, Glu298Asp, and intron 4b/a)
C
Comparator
Absence of these genetic variants / healthy volunteers
O
Outcome
Risk/prediction of coronary artery spasm

The eNOS T-786->C mutation is a strong independent genetic risk factor for coronary artery spasm, with effects that are potentially additive to cigarette smoking.

Cite This Study

Yoshimura et al. (2000) studied this question. The eNOS gene T −786 →C mutation is the strongest independent risk factor for coronary spasm, followed by smoking, hypertension, and Glu298Asp variant.

synapsesocial.com/papers/698d6e1a5be6419ac0d537a9https://doi.org/10.1177/108155890004800512
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Smoking is a risk factor for coronary spasm in young women.1992 · 121 citations
  2. 2Coronary-Artery Spasm1978 · 501 citations
  3. 3Multivessel coronary spasm in patients with variant angina: a study with intracoronary injection of acetylcholine.1988 · 221 citations
  4. 4T −786 →C Mutation in the 5′-Flanking Region of the Endothelial Nitric Oxide Synthase Gene Is Associated With Coronary Spasm1999 · 782 citations
  5. 5Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension1998 · 525 citations