IFNG and IFNGR1 gene polymorphisms and susceptibility to post-kala-azar dermal leishmaniasis in Sudan

Abstract

Post kala-azar dermal leishmanaisis (PKDL) in Sudan is associated with elevated interferon-γ. To study interferon-γ pathways in PKDL, we genotyped 80 trios from the Masalit ethnic group for polymorphisms at −470 ins/delTT, -270T/C, -56T/C and +95T/C in IFNGR1, and at −179G/A and +874T/A in IFNG. No associations occurred at IFNG. Global association with haplotypes comprising all 4 markers at IFNGR1 (χ2 10df = 21.97, P=0.015) was observed, associated with a significant (χ2 1df=4.54, P=0.033) bias in transmission of the haplotype insTT T T T, and less (χ2 1df=5.59, P=0.018) than expected transmission of insTT C C C. When compared with data on malaria associations from The Gambia, the results suggest a complex pattern of haplotypic variation at the IFNGR1 promoter locus associated with different infectious disease in African populations that reflect the complex roles of IFN-γ in parasite killing versus inflammation and pathogenesis.