Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Eur J Clin Microbiol Infect Dis. 2010 Oct;29(10):1291-5. doi: 10.1007/s10096-010-0985-0. Epub 2010 Jun 11.
Cytokines are crucial in activation of the cell-mediated immunity required for eliminating pathogens and controlling intracellular growth of Mycobacterium tuberculosis (TB). Genetic variants in the IL12-IFNG axis are hypothesized to be involved in the development and progression of TB. Genetic polymorphisms of rs2243115 and rs568408 in IL12A, rs3212227 in IL12B and rs2430561 in IFNG(+874) were detected in 522 pulmonary TB cases and 527 controls recruited from Yangzhong and Wujin County of China. It was found that genetic variants TG/GG of rs2243115(IL12A) were associated with a decreased risk of TB, with odds ratio (95% confidence interval) of 0.70 (0.49-0.99), whereas variant genotypes AT/TT of rs2430561(IFNG) conferred 82% less risk for treatment failure, with a hazard ratio of 0.18 (95% confidence interval 0.04-0.73). Cumulative effects analysis revealed that the risk of TB increased significantly with the number of unfavorable genotypes in IL12 genes. Furthermore, MDR analysis showed potential higher-order gene-gene and gene-environment interactions and indicated different outcomes based on distinct genotype profiles. Results from this study demonstrate that genetic polymorphisms of the IL12-IFNG pathway may individually or jointly contribute to the susceptibility to and prognosis of pulmonary TB.
细胞因子在激活细胞介导的免疫中至关重要，这对于消除病原体和控制结核分枝杆菌（TB）的细胞内生长至关重要。IL12-IFNG 轴的遗传变异被假设参与了 TB 的发展和进展。在中国的扬中和武进县招募了 522 例肺结核病例和 527 例对照，检测了 IL12A 中的 rs2243115 和 rs568408、IL12B 中的 rs3212227 和 IFNG(+874)中的 rs2430561 的遗传多态性。结果发现，rs2243115(IL12A)的遗传变异 TG/GG 与结核病风险降低相关，比值比（95%置信区间）为 0.70（0.49-0.99），而 rs2430561(IFNG)的变异基因型 AT/TT 则使治疗失败的风险降低了 82%，风险比为 0.18（95%置信区间 0.04-0.73）。累积效应分析显示，随着 IL12 基因中不利基因型数量的增加，结核病的风险显著增加。此外，MDR 分析显示，基因-基因和基因-环境之间存在潜在的更高阶相互作用，并根据不同的基因型谱显示出不同的结果。本研究的结果表明，IL12-IFNG 通路的遗传多态性可能单独或共同导致肺结核的易感性和预后。
