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Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy

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Abstract

Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02–1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14–3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.

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Authors and Affiliations

  1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Li Zhao, Bing Han, Lixin Wang, Yuming Sun, Xiaojun Lu, Chunyan Huang, Bin Tan, Chunxia Chen & Li Qin

  2. Department of Laboratory Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China

    Li Zhao

  3. Department of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Huanling Zhu

Authors
  1. Li Zhao
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  2. Huanling Zhu
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  3. Bing Han
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  4. Lixin Wang
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  5. Yuming Sun
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  6. Xiaojun Lu
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  7. Chunyan Huang
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  8. Bin Tan
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  10. Li Qin
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Contributions

Li Zhao and Chunxia Chen performed the research. Li Zhao and Li Qin designed the research study. Xiaojun Lu, Huanling Zhu, and Yuming Sun contributed essential reagents or tools. Li Zhao, Lixin Wang, Bing Han, and Bin Tan analyzed the data. Li Zhao and Chunyan Huang wrote the paper.

Corresponding author

Correspondence to Li Qin.

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All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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The authors declare that they have no conflict of interest.

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Zhao, L., Zhu, H., Han, B. et al. Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy. Ann Hematol 97, 685–695 (2018). https://doi.org/10.1007/s00277-018-3227-7

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  • DOI: https://doi.org/10.1007/s00277-018-3227-7

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