The endothelial nitric oxide synthase gene -786T/C polymorphism is a predictive factor for reattacks of coronary spasm

Pharmacogenet Genomics. 2007 Aug;17(8):581-7. doi: 10.1097/01.fpc.0000239978.61841.1a.

Abstract

Objective: We previously found a -786T/C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase (eNOS) gene and reported that this polymorphism is strongly associated with coronary spasm. In this study, we examined whether the polymorphism is a prognostic marker in coronary spasm patients.

Methods and results: We examined the clinical courses of 201 consecutive patients with coronary spasm who were admitted to our institution: 146 patients with the -786T/T genotype; 50 patients with the -786C/T genotype; and five patients with the -786C/C genotype. The mean follow-up period was 76+/-60 months. All the patients took calcium channel blockers and/or nitrate during the follow-up period. In this study, no patients died due to a cardiac event. About 25 patients were readmitted owing to cardiovascular disease. Out of these 25 patients, 23 patients were readmitted owing to a reattack of coronary spasm. The -786C allele was significantly associated with readmission due to coronary spasm (P=0.0072, odds ratio: 3.37 in the dominant effect). Kaplan-Meier analysis revealed that the occurrence of readmission was significantly higher in the patients with the -786C allele than in the patients without the -786C allele (P=0.0079). Further, multiple logistic regression analysis revealed that the -786T/C polymorphism was an independent predictor for readmission due to reattack of coronary spasm (P=0.006; relative risk=3.590).

Conclusions: The eNOS -786C allele is an independent risk factor for readmission due to a recurrent attack of coronary spasm in patients with coronary spasm, even if the patients have taken calcium channel blockers and/or nitrate.

MeSH terms

  • Adult
  • Aged
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / therapeutic use
  • Cause of Death
  • Coronary Artery Disease / enzymology
  • Coronary Artery Disease / genetics
  • Coronary Vasospasm / enzymology*
  • Coronary Vasospasm / genetics*
  • Cytosine*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Patient Readmission
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Recurrence
  • Risk Factors
  • Thymine*

Substances

  • Calcium Channel Blockers
  • Cytosine
  • Nitric Oxide Synthase Type III
  • Thymine