Variant Aldehyde Dehydrogenase 2 ( ALDH22 ) as a Risk Factor for Mechanical LA Substrate Formation and Atrial Fibrillation with Modest Alcohol Consumption in Ethnic Asians

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2021-10, Vol.11 (11), p.1559
• Main Authors: 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, Pan, Szu-Hua, Wang, Shih-Wei, Hou, Charles Jia-Yin, Hung, Ta-Chuan, Yeh, Hung-I
• Format: Article
• Language: English
• Subjects: 4-hydroxynonenal (4-HNE); Adult; Aged; Alcohol; Alcohol Drinking - adverse effects; Alcohol use; Alcoholic beverages; aldehyde; Aldehyde dehydrogenase; aldehyde dehydrogenase 2 (ALDH2); Aldehyde Dehydrogenase, Mitochondrial - genetics; Antihypertensives; Asian people; Asian People - genetics; Atrial Fibrillation - etiology; Atrial Fibrillation - genetics; Blood pressure; Cardiac arrhythmia; Cardiovascular disease; Dehydrogenases; Diabetes; Drinking behavior; Electrocardiography; Enzymes; Ethanol; Female; Fibrillation; Gene polymorphism; Genetic diversity; Genetic Predisposition to Disease; Heart Atria - pathology; Heart failure; Humans; Hypertension; Lipid metabolism; Lipid peroxidation; Male; Middle Aged; peak atrial longitudinal strain (PALS); Polymorphism; Polymorphism, Single Nucleotide; Questionnaires; Risk Factors; strain rates
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11111559

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, = 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), < 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 < 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 P :