Chikao Iwai

Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction.

BACKGROUND Rupture of the fibrous cap of an atherosclerotic plaque is a key event that predisposes to acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) may contribute to weakening of the cap, which favors rupture. Stromelysin, a member of MMP family, is identified extensively in human coronary atherosclerotic lesions. It can degrade most of the constituents of extracellular matrix as well as activating other MMPs, which suggests that it may play an important role in plaque rupture. Recently, a common variant (5A/6A) in the promoter of the stromelysin gene has been identified. The 5A/6A polymorphism could regulate the transcription of the stromelysin gene in an allele-specific manner. METHODS AND RESULTS To investigate the relation between the 5A/6A polymorphism in the promoter of the stromelysin gene and AMI, we conducted a case-control study of 330 AMI patients and 330 control subjects. The prevalence of the 5A/6A+5A/5A genotype was significantly more frequent in the patients with AMI than in control subjects (48.8% vs 32.7%, P<0.0001). In logistic regression models, the odds ratio of the 5A/6A+5A/5A was 2.25 (95% CI, 1.51 to 3.35). The association of 5A/6A polymorphism with AMI was statistically significant and independent of other risk factors. CONCLUSIONS The 5A/6A polymorphism in the promoter of the stromelysin gene is a novel pathogenetic risk factor for AMI.

Arg389Gly polymorphism of the human β1-adrenergic receptor in patients with nonfatal acute myocardial infarction

BACKGROUND We sought to investigate the relation between the Arg389Gly polymorphism in the human beta1-adrenergic receptor (ADRB1) gene and acute myocardial infarction (AMI). It was previously reported that augmented sympathetic activity might play an important role as a trigger of AMI by enhanced hemodynamic or mechanical forces through ADRB1 activation. Recently, a common polymorphism has been identified at amino acid position 389 (Arg or Gly) of the human ADRB1, within a region important for receptor-Gs protein coupling and subsequent agonist-stimulated adenylyl cyclase activation. METHODS To investigate the relation between the Arg389Gly polymorphism in the ADRB1 gene and AMI, we genotyped 354 patients with AMI and 354 age- and sex-matched control subjects by use of polymerase chain reaction amplification and the restriction fragment length polymorphism analysis. RESULTS The prevalence of the Arg389 homozygote (CC) genotype was significantly more frequent in patients with AMI than in control subjects (68.1% vs 47.2%, P <.0001). In logistic regression models, the odds ratio (OR) of Arg389 homozygote (CC) versus Arg389Gly heterozygote (CG) + Gly389 homozygote (GG) genotypes between control subjects and patients with AMI was 2.86 (95% CI 1.92-4.26, P =.0001). The association of the Arg389Gly polymorphism of ADRB1 with AMI was statistically significant and independent of other risk factors. CONCLUSION Our findings suggest that the genotype of Arg389Gly polymorphism in the human ADRB1 gene is associated with AMI.

Systemic Endothelial Function Is Preserved in Men With Both Active and Inactive Variant Angina Pectoris

To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm.