Variant Aldehyde Dehydrogenase 2 (ALDH2*2) as a Risk Factor for Mechanical LA Substrate Formation and Atrial Fibrillation with Modest Alcohol Consumption in Ethnic Asians
Journal
Biomolecules
Journal Volume
11
Journal Issue
11
Date Issued
2021-11
Author(s)
Hung, Chung-Lieh
Sung, Kuo-Tzu
Chang, Shun-Chuan
Liu, Yen-Yu
Kuo, Jen-Yuan
Huang, Wen-Hung
Su, Cheng-Huang
Liu, Chuan-Chuan
Tsai, Shin-Yi
Liu, Chia-Yuan
Lee, An-Sheng
Wang, Shih-Wei
Hou, Charles Jia-Yin
Hung, Ta-Chuan
Yeh, Hung-I
Abstract
Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06-2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.
Subjects
4-hydroxynonenal (4-HNE); alcohol; aldehyde; aldehyde dehydrogenase 2 (ALDH2); atrial fibrillation (AF); peak atrial longitudinal strain (PALS); strain rates
4-hydroxynonenal (4-HNE); Alcohol; Aldehyde; Aldehyde dehydrogenase 2 (ALDH2); Atrial fibrillation (AF); Peak atrial longitudinal strain (PALS); Strain rates
Other Subjects
4 hydroxynonenal; alcohol; aldehyde dehydrogenase isoenzyme 2; liver enzyme; adult; alcohol consumption; arterial wall thickness; Article; atrial fibrillation; binge drinking; body mass; body surface; cholesterol blood level; controlled study; coronary artery disease; creatinine blood level; diastolic blood pressure; echocardiography; electrocardiogram; estimated glomerular filtration rate; female; genetic polymorphism; genotype; glucose blood level; heart left atrium; heart left ventricle ejection fraction; hemoglobin blood level; human; hypertension; major clinical study; middle aged; non insulin dependent diabetes mellitus; non-drinker; posterior wall thickness; prospective study; Septal wall thickness; single nucleotide polymorphism; speckle tracking echocardiography; structured questionnaire; systolic blood pressure; tissue Doppler imaging; triacylglycerol blood level; urea nitrogen blood level; waist circumference; drinking behavior; risk factor; Alcohol Drinking; Atrial Fibrillation; Humans; Polymorphism, Genetic; Risk Factors
Publisher
MDPI
Type
journal article