The Role of Alcohol Dehydrogenase 2 and Aldehyde Dehydrogenase 2 Genotypes in Alcohol-Induced Vasospasic Angina.

Abstract

Alcohol ingestion often provokes attacks in patients with vasospastic angina. Type 2 aldehyde dehydrogenase (ALDH2) deficiency, which is based on a single point mutation (Glu487Lys) of the ALDH2 gene, is common in the Japanese population, but rare among the Caucasian population. We investigated how the genotype of ALDH2 affects the characteristics of alcohol-induced vasospastic angina. Ninety-one patients with vasospastic angina who had ingested alcohol daily or occasionally were studied. Patients had been diagnosed as vasospastic angina by a provocation test with an intracoronary injection of ergonovine or acetylcholine during coronary angiography. The Glu487Lys mutation was detected by allele specific PCR. We interviewed the patients to obtain information concerning the relationship between alcohol ingestion and anginal attacks. Alcohol ingestion induced attacks in 16 of 66 patients without the Glu487Lys mutation, 8 of 22 in heterozygotes, and 1 of 3 in mutant homozygotes. The intervals between alcohol ingestion and the onset of anginal attacks were shorter in homozygotes (0.17 hours) and heterozygotes (1.5+/-0.6 hours) for ALDH2*2 than in normal homozygotes for ALDH2*1 (5.4+/-0.6 hours). The amount of ethanol which induced attacks was significantly greater in normal homozygotes than in homozygotes (11 ml) and heterozygotes (42.5+/-7.1 ml) for ALDH2*2 (96.1+/-13.4 ml in normal patients). The frequency of anginal attacks induced by alcohol ingestion did not differ between ALDH deficient and normal homozygotes. In ALDH deficient patients, however, anginal attacks were induced by a smaller amount of alcohol immediately after its ingestion. Thus, the ALDH2 genotype modifies the characteristics of the anginal attacks as a co-factor for the induction of vasospastic angina after alcohol ingestion.

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

“…9 We and others also reported that CSA was induced by alcohol drinking, particularly in those with AFS. 10,11 The present study demonstrates for the first time that the frequencies of the variant ALDH2*2 genotype and AFS are significantly higher in the CSA group than in the non-CSA group. Conversely, the frequencies of CSA and AFS were significantly higher in the variant ALDH2*2 group than in the wild ALDH2*1*1 group.…”

“…9 We and others have reported that CSA can be induced by alcohol ingestion, particularly in those with AFS. 10,11 However, the relationships of CSA with ADH1B and ALDH2 gene polymorphisms remain to be elucidated. In the present study, we investigated the association of polymorphisms of ADH1B and ALDH2 with CSA.…”

Alcohol Flushing and Positive Ethanol Patch Test in Patients with Coronary Spastic Angina: Possible Role of Aldehyde Dehydrogenase 2 Polymorphisms

“…About half of East Asians show rapid and intense alcohol flushing after drinking alcohol in the amount that has no effect on Caucasians (6-8). We and others have shown that CSA could be induced by alcohol ingestion (9)(10)(11).…”

“…East Asians have been shown to have a mutation of the ALDH2*2 gene that leads to a reduced activity and intolerance to alcohol (ethanol) ingestion in about half of the population (5)(6)(7)(8). We and others have reported that CSA is induced by alcohol ingestion, particularly in those who have alcohol flushing upon alcohol intake (9)(10)(11). However, the relationship between alcohol intake and CSA has not been elucidated.…”

Association between Carotid Intima-media Thickness and Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism in Chinese Han with Essential Hypertension

“…People carrying the mutations have a low tolerability to alcohol and are at higher risk of developing cardiovascular diseases and of elevated blood pressure. [ 7 8 ]…”