# Association between ALDH2 rs671 polymorphism and susceptibility to non-valvular atrial fibrillation in a Chinese population: a large-scale case–control study

**Authors:** Fangming Zhong, Qifeng Zhang, Zhuolian Ye, Xuebo He, Junping Huang, Leiming Miao

PMC · DOI: 10.3389/fphys.2025.1669815 · 2026-02-03

## TL;DR

This study finds that a genetic variant in ALDH2 is linked to a higher risk of non-valvular atrial fibrillation in a Chinese population.

## Contribution

The study identifies ALDH2 rs671 polymorphism as an independent risk factor for non-valvular atrial fibrillation in a large Chinese cohort.

## Key findings

- The A allele of ALDH2 rs671 is associated with increased risk of non-valvular atrial fibrillation (OR = 1.472).
- GA and AA genotypes of ALDH2 rs671 are independent risk factors for non-valvular atrial fibrillation.
- The association remains robust across multiple propensity score-matched cohorts.

## Abstract

Non-valvular atrial fibrillation (NVAF) is the most common arrhythmia worldwide, with a steadily rising incidence and prevalence, posing a significant public health burden. Oxidative stress is recognized as a key driver of atrial remodeling and arrhythmogenesis. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a critical role in detoxifying reactive aldehydes, and the rs671 single-nucleotide polymorphism (G→A, Glu504Lys) markedly reduces enzymatic activity, with a high prevalence in East Asian populations. In this retrospective study, we analyzed 403 NVAF patients and 14,326 hospitalized controls from Meizhou People’s Hospital (2016–2020), aged ≥30 years (1:35.5 ratio), and constructed multiple propensity score-matched cohorts (1:15 to 1:2) to examine the association between ALDH2 rs671 and NVAF. The A allele frequency was significantly higher in NVAF patients than in the controls (32.0% vs. 24.2%, P < 0.001), causing an increased NVAF risk (OR = 1.472, 95% CI: 1.266–1.711). Multivariate logistic regression identified the GA genotype (OR = 1.681, 95% CI: 1.360–2.078, P < 0.001) and the AA genotype (OR = 1.558, 95% CI: 1.058–2.296, P = 0.025) as independent risk factors. Sensitivity analyses across various matching ratios confirmed the robustness of the association. Other independent risk factors included male sex, advanced age, hypertension, diabetes, coronary heart disease, and COPD.

## Linked entities

- **Genes:** ALDH2 (aldehyde dehydrogenase 2 family member) [NCBI Gene 217]
- **Diseases:** diabetes (MONDO:0005015), coronary heart disease (MONDO:0005010), COPD (MONDO:0005002)

## Full-text entities

- **Genes:** ALDH2 (aldehyde dehydrogenase 2 family member) [NCBI Gene 217] {aka ALDH-E2, ALDHI, ALDM}
- **Diseases:** unstable angina pectoris (MESH:D000789), ventricular tachycardia (MESH:D017180), arrhythmic (OMIM:212500), acute pulmonary embolism (MESH:D011655), ion channel dysregulation (MESH:D021081), neurological dysfunction (MESH:D009461), myocarditis (MESH:D009205), Stroke (MESH:D020521), cardiomyocyte dysfunction (MESH:D006331), Hyperthyroidism (MESH:D006980), mitral stenosis (MESH:D008946), COPD (MESH:D029424), hypertrophic cardiomyopathy (MESH:D002312), arrhythmia (MESH:D001145), Heart failure (MESH:D006333), III/IV (MESH:D006011), obesity (MESH:D009765), left ventricular dysfunction (MESH:D018487), obstructive ventilatory dysfunction (MESH:D012131), TIA (MESH:D002546), congenital heart disease (MESH:D006330), toxicity (MESH:D064420), Diabetes (MESH:D003920), Atrial fibrillation (MESH:D001281), valvular heart disease (MESH:D006349), end-stage renal disease (MESH:D007676), stable angina pectoris (MESH:D060050), MI (MESH:D009203), dilated cardiomyopathy (MESH:D002311), cardiovascular and cerebrovascular disorders (MESH:D002318), mitochondrial injury (MESH:D028361), Coronary heart disease (MESH:D003327), III/ (MESH:C537189), Hypertension (MESH:D006973), atrial arrhythmogenesis (MESH:D064752), end-stage liver disease (MESH:D058625), atrial flutter (MESH:D001282)
- **Chemicals:** blood glucose (MESH:D001786), aldehyde (MESH:D000447), ROS (MESH:D017382), alcohol (MESH:D000438), 4-HNE (MESH:C027576), acetaldehyde (MESH:D000079), agarose (MESH:D012685), lipid (MESH:D008055), EDTA (MESH:D004492), I131 (MESH:C000614965)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Glu504Lys, G-to-A

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909160/full.md

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Source: https://tomesphere.com/paper/PMC12909160