Objective: Reactive oxygen species (ROS) play a major role in the nonspecific innate immune response to invading microorganisms, such as Mycobacterium tuberculosis (MTB). Gp91phox, encoded by CYBB, serves as a key functional subunit of the Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase complex, which is pivotal to ROS generation. Therefore, the aim of the study was to investigate the association of CYBB polymorphisms with tuberculosis (TB) susceptibility.
Methods: In total, 636 TB patients and 608 healthy, age and gender matched controls were enrolled in this study. All subjects were unrelated ethnic Han Chinese. Two tagSNPs were selected from the HapMap database and genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry.
Results: After adjusting for confounders including age, gender and smoking, rs5917471 allele T showed significant association with decreased risk of TB (OR 0.745, 95% CI 0.556-0.999) and pulmonary TB (OR 0.618, 95% CI 0.410-0.931). However, no difference in allelic distribution was observed for the rs6610650 G/A polymorphism with respect to TB or different clinical types of TB. Further stratified analyses demonstrated the protective effect of allele T of rs5917471 was stronger among males (OR 0.500, 95% CI 0.295-0.846), smokers (OR 0.462, 95% CI 0.239-0.896), and male smokers (OR 0.372, 95% CI 0.182-0.761); the individuals carrying the A allele of rs6610650 exhibited an decreased risk of TB among males, smokers and male smokers, with OR (95% CI) of 0.535 (0.290-0.984), 0.442 (0.198-0.988), and 0.350 (0.145-0.845), respectively. There were no statistically significant differences in haplotype distribution between TB and control groups. Smoking and rs5917471 formed the best gene-environment interaction model with the testing balanced accuracy of 53.29% and cross-validation consistency of 9/10.
Conclusions: This is the first study of the association of CYBB polymorphisms with TB. Our findings suggest that the CYBB polymorphisms are significantly correlated with reduced risk of TB, especially among male smokers. Further studies are needed to verify this association.
Keywords: CYBB; Nicotinamide Adenine Dinucleotide Phosphate oxidase complex; Polymorphism; Reactive oxygen species; Susceptibility; Tuberculosis.
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