title: FOXO3A regulatory polymorphism and susceptibility to severe malaria in Gabonese children.
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.
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074, Tübingen, Germany, christiannguetse@gmail.com.
authors.forename: Christian Ngouadjio
authors.initials: CN
authors.lastname: Nguetse
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Thirumalaisamy P
authors.initials: TP
authors.lastname: Velavan
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology; D005681:Gabon; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007438:Introns; D016778:Malaria, Falciparum / Q000235:genetics* / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors