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FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population

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Abstract

It is well known that the human innate immune and adaptive immune response play important role in tuberculosis (TB) infection and progress. Emerging evidence shows that FOXO3 plays an important role in the human immune system. Recent research has shown that the FOXO3 genetic variants are associated malaria infection. In this study, 268 confirmed TB patients, 321 patients with latent tuberculosis infection (LTBI), and 475 TB-free controls were recruited; the single-nucleotide polymorphism (SNP) rs12212067: T > G in FOXO3 was genotyped using predesigned TaqMan® allelic discrimination assays. The results showed that the G allele of rs12212067 in FOXO3 was more common in health control and the latent TB group compared with the active TB group (p = 0.048, odds ratio (OR) 95 % confidence intervals (CI) = 1.37 (1.00–1.89); p = 0.042, OR 95 % CI = 1.42 (1.01–1.99), respectively); furthermore, within active TB patients, the G allele of rs12212067 in FOXO3 was more frequent in extra-pulmonary tuberculosis (EPTB) group compared to pulmonary tuberculosis (PTB) group (p = 0.035, OR 95 % CI = 0.57 (0.33–0.97). In conclusion, this study found that rs12212067 in FOXO3 was associated with increased risk of active TB. The minor G allele might be a protection factor which was found more common in latent TB patients and healthy controls than active TB patients.

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References

  1. Trajman, A., R.E. Steffen, and D. Menzies. 2013. Interferon-gamma release assays versus tuberculin skin testing for the diagnosis of latent tuberculosis infection: an overview of the evidence. Pulmonary Medicine 2013: 601737.

    PubMed Central  CAS  PubMed  Google Scholar 

  2. van der Eijk, E.A., E. van de Vosse, J.P. Vandenbroucke, and J.T. van Dissel. 2007. Heredity versus environment in tuberculosis in twins: the 1950s United Kingdom Prophit Survey Simonds and Comstock revisited. American Journal of Respiratory and Critical Care Medicine 176: 1281–1288.

    Article  PubMed  Google Scholar 

  3. Azad, A.K., W. Sadee, and L.S. Schlesinger. 2012. Innate immune gene polymorphisms in tuberculosis. Infection and Immunity 80: 3343–3359.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Comstock, G.W. 1978. Tuberculosis in twins: a re-analysis of the Prophit survey. The American Review of Respiratory Disease 117: 621–624.

    CAS  PubMed  Google Scholar 

  5. Cooke, G.S., S.J. Campbell, S. Bennett, et al. 2008. Mapping of a novel susceptibility locus suggests a role for MC3R and CTSZ in human tuberculosis. American Journal of Respiratory and Critical Care Medicine 178: 203–207.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Thye, T., F.O. Vannberg, S.H. Wong, et al. 2010. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. Nature Genetics 42: 739–741.

    Article  CAS  PubMed  Google Scholar 

  7. Png, E., B. Alisjahbana, E. Sahiratmadja, et al. 2012. A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians. BMC Medical Genetics 13: 5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Hosaka, T., W.H. Biggs 3rd, D. Tieu, et al. 2004. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proceedings of the National Academy of Sciences of the United States of America 101: 2975–2980.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Huang, H., and D.J. Tindall. 2007. Dynamic FoxO transcription factors. Journal of Cell Science 120: 2479–2487.

    Article  CAS  PubMed  Google Scholar 

  10. Maiese, K., Z.Z. Chong, J. Hou, and Y.C. Shang. 2009. The “O” class: crafting clinical care with FoxO transcription factors. Advances in Experimental Medicine and Biology 665: 242–260.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kerdiles, Y.M., D.R. Beisner, R. Tinoco, et al. 2009. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nature Immunology 10: 176–184.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Coffer, P.J., and B.M. Burgering. 2004. Forkhead-box transcription factors and their role in the immune system. Nature Reviews Immunology 4: 889–899.

    Article  CAS  PubMed  Google Scholar 

  13. Birkenkamp, K.U., and P.J. Coffer. 2003. FOXO transcription factors as regulators of immune homeostasis: molecules to die for? Journal of Immunology 171: 1623–1629.

    Article  CAS  Google Scholar 

  14. Dejean, A.S., D.R. Beisner, I.L. Ch’en, et al. 2009. Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells. Nature Immunology 10: 504–513.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Watkins, S.K., Z. Zhu, E. Riboldi, et al. 2011. FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer. The Journal of Clinical Investigation 121: 1361–1372.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Litvak, V., A.V. Ratushny, A.E. Lampano, et al. 2012. A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses. Nature 490: 421–425.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Willcox, B.J., T.A. Donlon, Q. He, et al. 2008. FOXO3A genotype is strongly associated with human longevity. Proceedings of the National Academy of Sciences of the United States of America 105: 13987–13992.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Lee, J.C., M. Espeli, C.A. Anderson, et al. 2013. Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell 155: 57–69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. 2000. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. American Journal of Respiratory and Critical Care Medicine 161: 1376–1395.

  20. Loparev, V.N., M.A. Cartas, C.E. Monken, A. Velpandi, and A. Srinivasan. 1991. An efficient and simple method of DNA extraction from whole blood and cell lines to identify infectious agents. Journal of Virological Methods 34: 105–112.

    Article  CAS  PubMed  Google Scholar 

  21. Bozzano, F., F. Marras, and A. De Maria. 2014. Immunology of tuberculosis. Mediterranean Journal of Hematology and Infectious Diseases 6, e2014027.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Hedrick, S.M., R. Hess Michelini, A.L. Doedens, A.W. Goldrath, and E.L. Stone. 2012. FOXO transcription factors throughout T cell biology. Nature Reviews Immunology 12: 649–661.

    Article  CAS  PubMed  Google Scholar 

  23. Haoues, M., A. Refai, A. Mallavialle, et al. 2014. Forkhead box O3 (FOXO3) transcription factor mediates apoptosis in BCG-infected macrophages. Cellular Microbiology 16: 1378–1390.

    Article  CAS  PubMed  Google Scholar 

  24. Sullivan, J.A., E.H. Kim, E.H. Plisch, S.L. Peng, and M. Suresh. 2012. FOXO3 regulates CD8 T cell memory by T cell-intrinsic mechanisms. PLoS Pathogens 8, e1002533.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Dejean, A.S., S.M. Hedrick, and Y.M. Kerdiles. 2011. Highly specialized role of Forkhead box O transcription factors in the immune system. Antioxidants & Redox Signaling 14: 663–674.

    Article  CAS  Google Scholar 

  26. van Grevenynghe, J., F.A. Procopio, Z. He, et al. 2008. Transcription factor FOXO3a controls the persistence of memory CD4(+) T cells during HIV infection. Nature Medicine 14: 266–274.

    Article  PubMed  Google Scholar 

  27. Crossley, L.J. 2003. Neutrophil activation by fMLP regulates FOXO (forkhead) transcription factors by multiple pathways, one of which includes the binding of FOXO to the survival factor Mcl-1. Journal of Leukocyte Biology 74: 583–592.

    Article  CAS  PubMed  Google Scholar 

  28. Jonsson, H., P. Allen, and S.L. Peng. 2005. Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis. Nature Medicine 11: 666–671.

    Article  CAS  PubMed  Google Scholar 

  29. Seiler, F., J. Hellberg, P.M. Lepper, et al. 2013. FOXO transcription factors regulate innate immune mechanisms in respiratory epithelial cells. Journal of Immunology 190: 1603–1613.

    Article  CAS  Google Scholar 

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    Authors and Affiliations

    1. Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefangdadao, Wuhan, 430030, China

      Yanjun Lu, Yaowu Zhu, Xiong Wang, Feng Wang, Jing Peng, Hongyan Hou & Ziyong Sun

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    1. Yanjun Lu
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    Correspondence to Ziyong Sun.

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    Yanjun Lu and Yaowu Zhu contributed equally to this work.

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    Lu, Y., Zhu, Y., Wang, X. et al. FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population. Inflammation 39, 10–15 (2016). https://doi.org/10.1007/s10753-015-0217-y

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