TNF-α rs1800629 Polymorphism in Vietnamese COPD Patients: Exploratory Evidence for Recessive Protective Association and Clinical Correlates

Background: Chronic obstructive pulmonary disease (COPD) poses a significant health burden in Vietnam. The TNF-α rs1800629 (− 308G/A) polymorphism is an influential factor in disease pathogenesis. However, its association is inconsistent across the studied populations. This study addresses this gap in Vietnam by examining allele frequencies and clinical associations in stable COPD patients. Methods: A cross-sectional study recruited 320 healthy controls and 266 stable COPD patients (per GOLD 2023 criteria) from October 2024 to August 2025. Clinical data were collected from medical records and direct interrogation. Genotyping was performed using PCR-RFLP. The dataset used for sensitivity analyses (2,660 observations) was created through multiple imputations to address missing clinical data. Associations of the rs1800629 with disease susceptibility and selected clinical management parameters were analyzed using Chi-square/Fisher’s exact tests, multivariable logistic regression, and sensitivity analysis. Results: The A allele frequencies were 8.83% (COPD), 6.88% (controls), and 7.77% overall ( p > 0.05). Patients were predominantly male smokers over 40 years, with moderate-severe symptoms (CAT ≥ 10, mMRC 3) and A/B severity groups. Under a recessive model, the AA genotype was associated with ~96% reduced susceptibility (adjusted OR 0.039, 95% CI 0.002– 0.62, p=0.022). Regression identified smoking (OR 1.83– 2.35), family history (OR 2.04), and onset ≥ 40 years (OR 2.88– 3.36) as independent symptom influences. Sensitivity analysis further supported the protective effect of the AA genotype and revealed GA protective effects on symptomatic outcomes (OR< 1, p < 0.05). Conclusion: Our findings suggest a possible protective recessive association of the TNF-α rs1800629 (− 308G/A) polymorphism with COPD susceptibility, symptom burden, and exacerbation risk. However, the wide confidence intervals arising from the rarity of the AA genotype and the use of multiply imputed data mean these signals are exploratory. Larger multi‑center studies with comprehensive exposure assessment are needed to confirm these observations. Keywords: COPD, TNF-α, rs1800629, polymorphism, Vietnam