East Asian Variant of Aldehyde Dehydrogenase 2 Is Associated With Coronary Spastic Angina

Abstract

Background-Coronary spastic angina (CSA) is a common disease among East Asians, including Japanese. The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is prevalent among East Asians. We examined whether CSA is associated with the 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 years). They were divided into CSA (112 patients) and control groups (90 patients). 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 sex, ALDH2*2 genotype carriers, alcohol flushing syndrome, 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 high-density lipoprotein cholesterol levels were lower (P<0.001) in the CSA group than in 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. (Circulation.

Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese

“…Contrary to our expectation based on the function of ALDH2 in reducing oxidative stress, the low frequency of the dysfunctional A allele of ALDH2 in patients with AF was an unexpected result. This is in contrast with the reports that the ALDH2 dysfunctional A allele was associated with coronary spastic angina and ischemic stroke in Ease Asian populations [22, 23]. We also noticed that in our study, frequency of ischemic heart diseases was higher in AF patients with AA and GA genotypes than those with the GG genotype-.…”

Parallel comparison of risk factors between progression of organic stenosis in the coronary arteries and onset of acute coronary syndrome by covariance structure analysis

“…Second, cigarette smoking and alcohol intake might have been underestimated in this study. It is probable that these two factors are linked more strongly to the onset of ACS because they often enhance the activity of coronary spasms in the Japanese [7,15,16]. Third, although we believe that the current path model provides new information, especially regarding the importance of MDA-LDL in ACS, the square of the multiple correlation coefficient was 0.086 for organic stenosis as an estimated value and 0.107 for ACS.…”

“…Recently, the importance of inflammation and collagen metabolism has been recognized [14]. In addition, it is hypothesized that coronary spasm contributes to the onset of ACS to a greater or lesser degree in most cases [7, 15–17]. Nevertheless, patients occasionally do not experience ACS attacks despite the extensive progression of organic stenosis or calcification in the coronary arteries.…”

Vasospastic angina: pathophysiology and clinical significance

“…Последние представлены катехоламинами (адреналин, норэпинефрин, дофамин, добутамин), парасимпатомиметическими (АХ, метахолин, пилокарпин) и антихолинэстеразными (физостигмин, галантамин, прозерин) препаратами, а также эргоновином, серотонином, гистамином, бета-адреноблокаторами, триптаном, кокаином, этиловым спиртом. Употребление алкоголя провоцирует СКА, особенно часто у лиц с реакцией "прилива алкоголя" [20].…”

“…У женщин с ВС в постменопаузе эстрогены усиливают антиокислительный потенциал, активность эндотелиальной NO-синтазы и подавляют СКА [27]. ВС ассоциируется также с полиморфизмом генов, кодирующих синтез медиаторов, обладающих антиокислительным действием, включая ALDH2, параоксоназу 1, стромелизин-1, интерлейкин-6 и фосфолипазу Cδ1 [2,3,20].…”