Cutaneous leishmaniasis remains one of the most important neglected tropical diseases. It is prevalent in Pakistan where its presence has been reported from all provinces. Apart from Leishmania species and Phlebotomus sandfly vector, host genetic factors also influence the severity and outcome of infection. This study explored 2 host genetic elements (SLC11A1 and CCR5) to assess their role in cutaneous leishmaniasis. SLC11A1 codes for the solute carrier transmembrane protein that is directly involved in the restriction of Leishmania parasites within macrophages. Genetic association studies of SLC11A1 suggest its role in predisposition to leishmaniasis. However, recent reports fail to support this association. CCR5 is translated into CC chemokine receptor 5 that seems to play a dual role during leishmaniasis. It helps the parasites to persist within the host, extending the infection, while at the same time assists HIV entry into immune cells. This leads to Leishmania/HIV-coinfection, a complexity that seems to have risen in the last decade or so. The current study analyzed a total of 393 individuals including 274 cutaneous leishmaniasis cases and 119 uninfected controls exposed to the same environment. Results reveal a higher incidence of infection among males (70%), possibly due to a higher exposure to the sandfly while the most affected age group were children 15 years or younger. Single loci and haplotype analysis of 8 genetic variations of SLC11A1 revealed no association with susceptibility to cutaneous leishmaniasis. These results hold importance because they question the significance of SLC11A1 as a candidate susceptibility gene particularly in this region since other Asian countries have reported similar results. No significant association was observed for the HIV-protective CCR5Δ32 allele and leishmaniasis as well. This low frequency of Δ32 allele exposes the population to a higher risk of HIV and hence co-infection. Incidentally, the prevalent wildtype CCR5 reinforces its supportive role in disease progression. However, five Δ32 homozygotes were identified which have not yet been reported from Pakistan. The geographical distribution of Δ32 allele was significantly higher in Khyber Pakhtunkhwa province as compared to the rest of the country. Hence, this study presents new insights and understandings into cutaneous leishmaniasis at the genetic level.
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