IFNG and IFNGR1 gene polymorphisms and susceptibility to post-kala-azar dermal leishmaniasis in Sudan
Genes and Immunity, Volume 8, No. 1, Year 2007
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Post-kala-azar dermal leishmanaisis (PKDL) in Sudan is associated with elevated interferon-γ (IFN-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 four markers at IFNGR1 (χ210df=21.97, P=0.015) was observed, associated with a significant (χ21df=4.54, P=0.033) bias in transmission of the haplotype insTT T T T and less (χ21df=5.59, P=0.018) than expected transmission of insTT C C C. When compared with data on malaria associations from 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.