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FOXO3A regulatory polymorphism and susceptibility to severe malaria in Gabonese children

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Abstract

The clinical course of malaria varies between affected individuals and host genetic factors have been shown to influence the outcome of malaria. The role of FOXO3-driven pathway in modulating inflammatory responses, including mediation of distinct functions of regulatory T effector cell populations (Tregs) by the transcription factor FOXO3, has recently been recognized. We aimed to study possible associations of a non-coding polymorphism in intron 2 of the FOXO3A gene (rs12212067T>G) that was shown earlier to modulate the FOXO3 expression and to be associated with the prognosis of distinct inflammatory and infectious diseases. The FOXO3A polymorphism rs12212067T>G was genotyped by direct sequencing in a group of Gabonese children with confirmed Plasmodium falciparum malaria. Severe cases of malaria were compared with asymptomatic/mild cases. The FOXO3A variant rs12212067T>G was associated with the phenotype of severe malaria, but not with asymptomatic/mild malaria (allelic model: OR = 1.54, 95 % CI = 1.15–2.05, P = 0.0028; dominant model: OR = 1.94, 95 % CI = 1.36–2.77, P = 0.0002). The FOXO3A variant rs12212067T>G is associated with increased inflammatory responses to Plasmodium falciparum malaria, indicating a role of the FOXO3-dependent pathway in malaria.

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Acknowledgments

We would like to thank the staff and technicians of Lambaréné, Gabon, for their assistance in collecting the blood samples of patients during the study. We also express our gratitude to all the study participants involved in this study.

Conflicts of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074, Tübingen, Germany

    Christian Ngouadjio Nguetse, Peter G. Kremsner & Thirumalaisamy P. Velavan

  2. Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon

    Peter G. Kremsner

  3. Fondation Congolaise pour la Recherche Médicale, Brazzaville, Republic of the Congo

    Thirumalaisamy P. Velavan

Authors
  1. Christian Ngouadjio Nguetse
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  2. Peter G. Kremsner
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  3. Thirumalaisamy P. Velavan
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Correspondence to Thirumalaisamy P. Velavan.

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Nguetse, C.N., Kremsner, P.G. & Velavan, T.P. FOXO3A regulatory polymorphism and susceptibility to severe malaria in Gabonese children. Immunogenetics 67, 67–71 (2015). https://doi.org/10.1007/s00251-014-0816-z

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  • DOI: https://doi.org/10.1007/s00251-014-0816-z

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