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TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso

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Abstract

We have previously obtained strong evidence for linkage of mild malaria attack to the MHC region, with a peak close to the tumor necrosis factor (TNF) gene. We screened, for polymorphisms, the entire TNF gene in the same sample of 34 families comprising 197 individuals living in a Plasmodium falciparum endemic area and we found 17 polymorphisms. In a longitudinal study, we investigated whether the 11 most frequent and informative polymorphisms were associated with mild malaria attack and maximum parasitemia, which was the highest parasitemia in each individual over 2 years. Mild malaria attack and maximum parasitemia were positively correlated. Transmission disequilibrium tests showed nominal evidence for association between TNF-1031, TNF-308, TNF851 and TNF1304 polymorphisms, and mild malaria attack on the one hand, and between TNF-238, TNF851 and TNF1304 polymorphisms, and maximum parasitemia on the other hand. After accounting for multiple tests, we confirmed the association of TNF-238 with maximum parasitemia and the association of TNF1304 and TNF851 with maximum parasitemia and mild malaria attack. The association tests with mild malaria attack suggest a moderate effect of TNF-308 polymorphism. In conclusion, our study suggests that several TNF variants may be part of the genetic determinants for maximum parasitemia and/or mild malaria attack.

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Acknowledgements

We thank all volunteer families of Bobo-Dioulasso. Assistance from the ‘Genome Variation’ (GenoVarior) core facilities from Marseille-Génopôle was greatly appreciated and we thank Jérôme Belougne for his technical help. This work was supported by the French Ministry of Research and Technology (PAL+ Program), the Fondation pour la Recherche Médicale, the PACA Conseil Régional and the Conseil Général des Bouches du Rhône. LF is supported by a studentship from the Fondation pour la Recherche Médicale and NFD is supported by a studentship from the French Ministry of Research and Technology.

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Authors and Affiliations

  1. Laboratoire d'immunogénétique et de pharmacologie du paludisme-EA 864, Faculté de Pharmacie, Université de la Méditerranée, Marseille, IFR 48, Cedex, France

    L Flori, N F Delahaye, F Fumoux & P Rihet

  2. International Livestock Research Institute, Nairobi, Kenya

    F A Iraqi & M Hernandez-Valladares

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  1. L Flori
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  2. N F Delahaye
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  3. F A Iraqi
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  4. M Hernandez-Valladares
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  5. F Fumoux
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  6. P Rihet
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Correspondence to P Rihet.

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Flori, L., Delahaye, N., Iraqi, F. et al. TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso. Genes Immun 6, 472–480 (2005). https://doi.org/10.1038/sj.gene.6364231

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  • DOI: https://doi.org/10.1038/sj.gene.6364231

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