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

L. Flori, N. F. Delahaye, F. A. Iraqi, M. Hernandez-Valladares, F. Fumoux, P. Rihet

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)472-480
Number of pages9
JournalGenes and Immunity
Volume6
Issue number6
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Association
  • Mild malaria attacks
  • P. falciparum
  • Parasitemia
  • Tumor necrosis factor genetic linkage

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