Liu Qianqian, Wang Jing, Sandford Andrew J, Wu Jingcan, Wang Yu, Wu Shouquan, Ji Guiyi, Chen Guo, Feng Yulin, Tao Chuanmin, He Jian-Qing
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Division of Infectious Diseases, People's Hospital of Aba Tibetan Autonomous Prefecture, Maer, Sichuan, China.
Infect Genet Evol. 2015 Jul;33:169-75. doi: 10.1016/j.meegid.2015.04.026. Epub 2015 Apr 27.
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.
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.
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.
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.
活性氧（ROS）在对入侵微生物（如结核分枝杆菌，MTB）的非特异性固有免疫反应中起主要作用。由CYBB编码的Gp91phox作为烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶复合物的关键功能亚基，对ROS的产生至关重要。因此，本研究的目的是调查CYBB基因多态性与结核病（TB）易感性的关联。
本研究共纳入636例TB患者和608例年龄、性别匹配的健康对照。所有受试者均为汉族无关个体。从HapMap数据库中选择两个标签单核苷酸多态性（tagSNP），并使用基质辅助激光解吸/电离飞行时间质谱进行基因分型。
在调整年龄、性别和吸烟等混杂因素后，rs5917471等位基因T与TB风险降低显著相关（OR 0.745，95%CI 0.556 - 0.999）以及肺结核风险降低相关（OR 0.618，95%CI 0.410 - 0.931）。然而，rs6610650 G/A多态性在TB或不同临床类型的TB中的等位基因分布未观察到差异。进一步的分层分析表明，rs5917471等位基因T在男性（OR 0.500，95%CI 0.295 - 0.846）、吸烟者（OR 0.462，95%CI 0.239 - 0.896）和男性吸烟者（OR 0.372，95%CI 0.182 - 0.761）中具有更强的保护作用；携带rs6610650 A等位基因的个体在男性、吸烟者和男性吸烟者中患TB的风险降低，OR（95%CI）分别为0.535（0.290 - 0.984）、0.442（0.198 - 0.988）和0.350（0.145 - 0.845）。TB组和对照组之间的单倍型分布没有统计学显著差异。吸烟和rs5917471形成了最佳的基因 - 环境相互作用模型，测试平衡准确率为53.29%，交叉验证一致性为9/10。
这是第一项关于CYBB基因多态性与TB关联的研究。我们的研究结果表明，CYBB基因多态性与TB风险降低显著相关，尤其是在男性吸烟者中。需要进一步研究来验证这种关联。
