Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 07 26 1 6 Kun Cheng Cardiovascular Surgery, Zibo Central Hospital, Zibo, Shandong, China Xuekai Zhao Cardiovascular Surgery, Zibo Central Hospital, Zibo, Shandong, China Sheng Wang Cardiovascular Surgery, Zibo Central Hospital, Zibo, Shandong, China Qixuan Zhai Cardiovascular Surgery, Zibo Central Hospital, Zibo, Shandong, China 2025 06 03 2026 02 16 This study aimed to investigate the association between tumor necrosis factor-α (TNF-α) gene polymorphisms and the risk of pulmonary infection following heart valve replacement surgery, while controlling for potential clinical confounders. A total of 200 patients who underwent heart valve replacement surgery between January 2022 and December 2024 were included. TNF-α genotyping was performed using TaqMan probe-based real-time quantitative PCR. Propensity score matching (PSM, 1:1) was applied to balance baseline characteristics such as age, sex, body mass index, comorbidities, and operative factors. Logistic regression and stratified analyses were used to assess the impact of genetic and clinical risk factors on postoperative pulmonary infection. After PSM, 51 matched pairs were analyzed. The TNF-α −308A allele (rs1800629) was significantly associated with an increased risk of pulmonary infection. Stratified analysis revealed that this genetic effect was more pronounced in male patients. The infection rate among carriers of the TNF-α −238A allele (rs361525) was 85.7%, significantly higher than that of the GG genotype (44.3%). Prolonged aortic cross-clamp time, extended cardiopulmonary bypass duration, and reduced left ventricular ejection fraction were identified as independent clinical risk factors. The TNF-α −308G/A polymorphism significantly increases the risk of pulmonary infection following heart valve replacement, particularly in patients with prolonged myocardial ischemia or impaired cardiac function. Preoperative genetic screening and optimization of surgical strategies may help reduce infection risk in high-risk individuals. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4478 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4478/2378