The Significance of Aldehyde Dehydrogenase 2 Polymorphisms in Coronary Spastic Angina

Introduction: Coronary spasm plays an important role in the pathogenesis of coronary heart disease and coronary spastic angina (CSA) is prevalent in East Asia including Japan. Oxidative stress is thought to be one of important factors in pathogenesis of coronary spasm. Interestingly, East Asians have been shown to have a frequent mutation of the aldehyde dehydrogenase 2 (ALDH2) gene (ALDH2*2) that leads to reducing of anti-oxidative effect and intolerance to alcohol ingestion (alcohol flushing). Furthermore, we previously reported that coronary spasm could be induced by alcohol intake in CSA patients. Hypothesis: We herein examined whether CSA is associated with ALDH2 polymorphisms by using single nucleotide polymorphism (SNP) genotyping method. Methods: The study subjects consisted of 155 patients in whom intracoronary injection of acetylcholine were performed on suspicion of coronary spastic angina. They were divided into 95 CSA patients (67 men/ 28 women, mean age 67 ± 10) and 60 non-CSA patients (26 men/ 34 women, mean age 65 ± 13). SNP genotyping test for ALDH2 along with clinical data for CSA risk factors were investigated.[[Unable to Display Character: 
]] Results: Gender (male), uric acid and smoking were higher (P = 0.001, P = 0.0014 and P = 0.001, respectively) and HDL cholesterol level was lower (P = 0.0021) in the CSA patients than in the non-CSA patients. There was a significant difference on the rate of CSA between ALDH2*1/*1 (wild type) and ALDH2*1/*2 or ALDH2*2/*2 (non-activated genotype) (51.2% vs. 73.2%, P = 0.005). Multivariable logistic regression analysis including age, ALDH2 non-activated genotype, smoking, and HDL cholesterol as independent variables revealed that ALDH2 non-activated genotype, HDL cholesterol and smoking were significant predictors of CSA (P = 0.007, P = 0.030 and P = 0.016, respectively). Furthermore, this study showed that ALDH2*2/*2 is a significant risk factor for CSA (90.9%) and multi-vessel spasm (80%).[[Unable to Display Character: 
]] Conclusions: ALDH2 non-activated genotype as well as smoking and HDL cholesterol, was significantly associated with CSA in Japanese patients.