ROLE OF IFN-γ AND IFNGR1 GENE POLYMORPHISMS IN SUSCEPTIBILTY TO POST KALA-AZAR DERMAL LEISHMANIASIS (PKDL) IN SELECTED SUDANESE POPULATION

Abstract

The aim of this study is to determine whether IFNGR1 and IFN-γ gene polymorphisms are associated with PKDL in the high susceptible Masalit tribe from three adjacent villages Um-salala, EL-Rugab and Ali babkir in eastern Sudan. DNA was prepared from 62 Trios and 32 pairs using Multiple Displacement Amplification (MDA) method. Four IFNGR1 polymorphisms; +95T/C, -56T/C, -270T/C and -470 ins/del and two IFN-γ polymorphisms; +874T/A and -179G/A were genotyped using ARMS-PCR and RFLP. The data were tested for their fit to Hardy- Weinberg equilibrium, and the polymorphisms were analyzed for their association to the disease using TDT, single point logistic regression analysis and Haplotype base score test. All polymorphisms are found in Hardy- Weinberg equilibrium. TDT analysis showed an evidence of association between PKDL and IFNGR1-270 polymorphism (P=0.023; X2=4.571). The haplotype base score test indicates that -270 polymorphism has separate main effect on PKDL (P=0.008). No evidence of association between other SNPs and susceptibility to PKDL. The frequency of IFN-γ polymorphism +874 allele was low among Masalit tribe (0.2). In conclusion -270T/C polymorphism may have functional affect or in linkage disequilibrium with other functional SNPs within IFNGR1 gene