Genetics and visceral leishmaniasis in the Sudan: seeking a link

With the human genome sequence in hand, emphasis is now focusing on genetic diversity and its role in susceptibility to disease. In the Sudan, different tribes share the same exposure to Leishmania donovani, but only certain tribes are at risk of clinical disease. This suggests that host genotype is important, with genes controlling innate and adaptive immunity likely to be involved. Using multicase families, linkage and allelic association has been demonstrated between clinical visceral leishmaniasis (VL) and the innate resistance gene SLC11A1 (formerly NRAMP1), which regulates macrophage activation. Polymorphism at IL4 is also associated with underlying susceptibility to VL, whereas IFNGR1 is associated specifically with post-kala-azar dermal leishmaniasis.