Variant Aldehyde Dehydrogenase 2 (ALDH2*2) in East Asians Interactively Exacerbates Tobacco Smoking Risk for Coronary Spasm. - Possible Role of Reactive Aldehydes

Background: Coronary spastic angina (CSA) is common among East Asians and tobacco smoking (TS) is an established risk factor for CSA. Aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing reactive toxic aldehydes and a deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined the interaction between TS and ALDH2*2 as a risk factor for CSA to better understand the disease pathogenesis. Methods and Results: The study subjects comprised 410 patients (258 men, 152 women; mean age, 66.3 +/- 11.5) in whom intracoronary injection of acetylcholine was performed on suspicion of CSA. ALDH2 genotyping was performed by direct application of the Taqman polymerase chain reaction system. Of the study subjects, 244 had CSA proven and 166 were non-CSA. The frequencies of male sex, ALDH2*2, alcohol flushing syndrome, TS, coronary organic stenosis, and plasma levels of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, and P=0.015, respectively) and that of high-density lipoprotein cholesterol lower (P=0.002) in the CSA than non-CSA group. Multivariable logistic regression analysis revealed that ALDH2*2 and TS were significant risk factors for CSA (P<0.001 and P=0.002, respectively). ALDH2*2 exacerbated TS risk for CSA more than the multiplicative effects of each. Conclusions: ALDH2*2 synergistically exacerbates TS risk for CSA, probably through aldehydes.