Synergistic interaction of T-786-->C polymorphism in the endothelial nitric oxide synthase gene and smoking for an enhanced risk for coronary spasm

Pharmacogenetics. 2003 Nov;13(11):683-8. doi: 10.1097/00008571-200311000-00004.

Abstract

Objective: We previously reported that a T-786-->C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase gene and smoking were independently associated with coronary spasm; however, the interaction between this polymorphism and smoking remains to be elucidated.

Methods: We analyzed 209 men and 238 women who were admitted consecutively at our institution; all subjects received an intracoronary injection of acetylcholine (ACh) while undergoing coronary angiography for evaluation of chest pain: all subjects had no significant coronary stenosis. We divided these subjects into four groups: non-smokers with T/T genotype (Control Group A); non-smokers with C/T or C/C genotype (Group B); smokers with T/T genotype (Group C); and smokers with C/T or C/C genotype (Group D). We further examined quantitative coronary angiographies of the left anterior descending coronary artery in a subset of 54 consecutive men and 53 consecutive women.

Results: The frequencies of coronary spasm in Group B (male: 61%, female: 78%), Group C (62%, 59%) and Group D (91%, 92%) were significantly higher than in Group A (30%, 38%). In the males, ACh-induced vasoconstriction was greatest in Group D, and the change was weakest in Group A. In the females, ACh-induced vasoconstrictions were significantly greater in Groups B, C and D than in Group A. The T-786-->C polymorphism and smoking combine to increase the risk of coronary spasm.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Aged
  • Asian People
  • Base Sequence / genetics
  • Coronary Vasospasm / genetics*
  • Female
  • Humans
  • Isosorbide Dinitrate / pharmacology
  • Logistic Models
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / genetics*
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies
  • Risk Factors
  • Smoking / adverse effects*
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Vasodilator Agents
  • Nitric Oxide Synthase
  • Isosorbide Dinitrate
  • Acetylcholine