DPF3 polymorphisms increased the risk of pulmonary tuberculosis in the Northwest Chinese Han population

•The rs202075571 and rs61986330 in DPF3 were associated with an increased risk of PTB.•DPF3-rs10140566 was associated with PTB risk in females, age ≤40, and non-smokers.•A multi-site model demonstrated significant potential for predicting the risk of PTB.•The DPF3 gene was highly expressed in PTB compared to healthy controls. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in DPF3 and susceptibility to pulmonary tuberculosis (PTB) in the Northwest Chinese Han population. Genotyping of four DPF3 SNPs (rs10140566, rs75575287, rs202075571, and rs61986330) was performed using Agena MassARRAY from 488 PTB patients and 488 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Multifactor dimensionality reduction (MDR) analysis was employed to investigate the effect of SNP-SNP interactions on PTB risk. The GSE54992 dataset was analyzed using R software to ascertain DPF3 expression levels. Overall analysis revealed that rs202075571 (allele: OR = 1.31, p = 0.015; CC vs. TT: OR = 1.97, p = 0.049; dominant: OR = 1.33, p = 0.032) and rs61986330 (allele: OR = 1.38, p = 0.010; CA vs. CC: OR = 1.35, p = 0.044; dominant: OR = 1.40, p = 0.019) were associated with an increased PTB risk. Stratified analysis showed that rs10140566 was a PTB risk factor in females, those aged ≤40 and non-smokers, and rs202075571 was associated with PTB risk in individuals aged >40 and smokers, and rs61986330 was associated with PTB risk in males, those aged >40 and smokers. The four SNPs model demonstrated significant predictive potential for PTB risk. Furthermore, DPF3 exhibited higher expression in PTB compared to healthy controls. DPF3 polymorphisms (rs10140566, rs202075571, and rs61986330) are associated with an increased risk of PTB, providing valuable new insights into the mechanism of PTB.