East Asian Variant of Aldehyde Dehydrogenase 2 (ALDH2*2) is Associated with Coronary Spastic Angina: Possible Roles of Reactive Aldehydes and Implications of Alcohol Flushing Syndrome
Background—Coronary spastic angina (CSA) is a common disease among East Asians including Japanese. The prevalence of alcohol flushing syndrome (AFS) associated with deficient activity of variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians. We examined whether CSA is associated with ALDH2*2 genotype in Japanese.
Methods and Results—The study subjects consisted of 202 patients in whom intracoronary injection of acetylcholine was performed by angiography on suspicion of CSA (119 men and 83 women, mean age 66.2±11.4). They were divided into CSA (112 patients) and control (90 patients) groups. ALDH2 genotyping was performed by the direct application of the TaqMan polymerase chain reaction system on dried whole blood. Clinical and laboratory data were examined using conventional methods. The frequencies of male gender, ALDH2*2 genotype carriers, AFS, tobacco smoking and the plasma level of uric acid were higher (P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.007, respectively) and the plasma HDL cholesterol levels were lower (P < 0.001) in the CSA group than the control group. The multivariable logistic regression analysis revealed that ALDH2*2 genotype and smoking were significantly associated with CSA (P < 0.001 and P = 0.024, respectively).
Conclusions—East Asian variant ALDH2*2 genotypes and hence deficient ALDH2 activity were associated with CSA in Japanese. These data support further investigation of treatment targeting aldehydes for CSA.
- aldehyde dehydrogenase 2
- coronary spastic angina
- coronary spasm
- ischemic heart disease
- alcohol dehydrogenase gene
- Received September 3, 2014.
- Revision received March 4, 2015.
- Accepted March 9, 2015.