Family-based association of a low producing lymphotoxin-alpha allele with reduced Plasmodium falciparum parasitemia.

Tumor necrosis factor (TNF)-related genes are thought to play a role in human malaria. TNF polymorphisms have been associated with severe malaria, mild malaria, and parasitemia. Lymphotoxin-alpha gene (LTA) that belongs to the TNF family is one such candidate gene. Here we report the family-based association analysis of a cis-regulatory lymphotoxin-alpha polymorphism with parasitemia in two independent populations living in Burkina Faso. Analysis of 199 subjects (34 families) living in an urban endemic area revealed the association of the low producing LTA+80A allele with reduced parasitemia. Furthermore, there was evidence of significant LTA+80-by-age and LTA+80-by-gender interactions. In another set of 318 residents (55 families) in a rural endemic area, we found both the association of the low producing LTA+80A allele with reduced parasitemia and LTA+80-by-age and LTA+80-by-gender interactions. This study suggests that LTA+80 polymorphism influences parasitemia and acts in an age- and gender-dependent manner.