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Association of genetic polymorphisms in the IL12-IFNG pathway with susceptibility to and prognosis of pulmonary tuberculosis in a Chinese population

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Abstract

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.

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Acknowledgements

This study was supported by the Natural Science Foundation of Jiangsu Province (BK2008447).

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Correspondence to J. Wang.

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Wang, J., Tang, S. & Shen, H. Association of genetic polymorphisms in the IL12-IFNG pathway with susceptibility to and prognosis of pulmonary tuberculosis in a Chinese population. Eur J Clin Microbiol Infect Dis 29, 1291–1295 (2010). https://doi.org/10.1007/s10096-010-0985-0

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  • DOI: https://doi.org/10.1007/s10096-010-0985-0

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