Child hospitalization due to severe malaria is associated with the ICAM-1 Kilifi allele but not adherence patterns of Plasmodium falciparum infected red blood cells to ICAM-1

Abstract

This study aimed at determining whether the predisposition of a mutation at position 179 of the ICAM-1 gene to child hospitalization due to malaria was mediated by changes in adherence properties of IRBCs to ICAM-1. ICAM-1 genotypes were determined by nested polymerase chain reaction of isolated DNA from filter blood spots followed by Restriction Fragment Length Polymorphism (RFLP). Plasmodium falciparum adherence assays were done on immobilized purified ICAM-1. Our data indicate that the homozygosity for the ICAM-1 Kilifi mutation occurs at a frequency of 22.3% in Magugu-Babati, Northern Tanzania. Our results show that there are no differences in IRBC binding profiles across genotypes. We show in this study that homozygosity for the ICAM-1 Kilifi is associated with child hospitalization ( X 2 = 14.47, p < 0.001). We have further shown that hospitalization was not associated with cytoadherence ( X 2 = 0.17, p = 0.68). We conclude that the ICAM-1 Kilifi allele occurs at a high frequency in Tanzania and that associations of this allele with higher child hospitalization frequencies is independent of cytoadherence patterns of IRBC isolated from ICAM-1 genotypes, implying that any associations reported to exist between the ICAM-1 Kilifi mutation and severe malaria are unlikely to be mediated through altered IRBC cytoadherence properties.