Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers

Takayoshi Yamashita; Yuichiro Arima; Tadashi Hoshiyama; Noriaki Tabata; Daisuke Sueta; Yusei Kawahara; Miwa Ito; Hisanori Kanazawa; Masanobu Ishii; Kenshi Yamanaga; Shinsuke Hanatani; Seiji Takashio; Satoshi Araki; Satoru Suzuki; Eiichiro Yamamoto; Koichi Kaikita; Kentaro Oniki; Junji Saruwatari; Kenichi Matsushita; Kenichi Tsujita

doi:10.1016/j.jacasi.2021.10.009

Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers

JACC Asia. 2022 Jan 18;2(1):62-70. doi: 10.1016/j.jacasi.2021.10.009. eCollection 2022 Feb.

Authors

Takayoshi Yamashita¹, Yuichiro Arima¹, Tadashi Hoshiyama¹, Noriaki Tabata¹, Daisuke Sueta¹, Yusei Kawahara¹, Miwa Ito¹, Hisanori Kanazawa¹, Masanobu Ishii¹, Kenshi Yamanaga¹, Shinsuke Hanatani¹, Seiji Takashio¹, Satoshi Araki¹, Satoru Suzuki¹, Eiichiro Yamamoto¹, Koichi Kaikita¹, Kentaro Oniki², Junji Saruwatari², Kenichi Matsushita¹, Kenichi Tsujita¹

Affiliations

¹ Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
² Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

Background: Alcohol-a risk factor for atrial fibrillation (AF)-is metabolized by aldehyde dehydrogenase 2 (ALDH2). Dysfunctional alleles of ALDH2 (ALDH2-deficient variants) are prevalent among East Asians.

Objectives: Because the prevalence of AF is estimated to be high in ALDH2-deficient variant carriers, we investigated the correlation between AF and ALDH2-deficient variant carriers, including the association with habitual alcohol consumption.

Methods: A total of 656 consecutive patients were included in this investigation. ALDH2 genotypes were divided into ALDH2 homozygous wild-type (∗1/∗1), ALDH2 heterozygous-deficient allele (∗1/∗2), and ALDH2 homozygous-deficient allele (∗2/∗2). Multivariate analyses were applied to determine the correlation between ALDH2 genotype and AF.

Results: ALDH2∗1/∗2 and ALDH2∗2/∗2 carriers who were ALDH2-deficient variant carriers comprised 199 (30.3%) and 27 (4.1%) patients, respectively. Among these patients, the proportions of habitual alcohol consumption were 26.1% and 0%, respectively. Multivariate analysis revealed that ALDH2∗1/∗2 itself was not a risk factor for AF (odds ratio [OR]: 1.28; P = 0.21). However, habitual alcohol consumption in ALDH2∗1/∗2 carriers was an independent risk factor of AF (OR: 4.13; P = 0.001). Contrary to expectations, ALDH2∗2/∗2 itself had a lower incidence of AF among other risk factors (OR: 0.37; P = 0.03).

Conclusions: Although the ALDH2∗1/∗2 itself was not associated with AF, ALDH2∗1/∗2 carriers with habitual alcohol consumption could experience AF because of slow alcohol metabolism. In contrast, ALDH2∗2/∗2 itself had a lower incidence of AF. This might be related to the absence to habitual alcohol consumption in ALDH2∗2/∗2 carriers because of the negligible activity of ALDH2. Thus, abstaining from alcohol consumption might prevent the development of AF in patients who are ALDH2∗1/∗2 carriers.

Keywords: AF, atrial fibrillation; ALDH2, aldehyde dehydrogenase 2; CI, confidence interval; ECG, electrocardiogram; East Asians; OR, odds ratio; alcohol; aldehyde dehydrogenase; atrial fibrillation.