TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso.
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.
Flori
L
L
Laboratoire d'immunogénétique et de pharmacologie du paludisme-EA 864, Faculté de Pharmacie, Université de la Méditerranée, IFR 48, Marseille Cedex, France.
Delahaye
N F
NF
Iraqi
F A
FA
Hernandez-Valladares
M
M
Fumoux
F
F
Rihet
P
P
D000483:Alleles; D002050:Burkina Faso; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000235:genetics*; D008297:Male; D018512:Parasitemia / Q000235:genetics*; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha