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  • Title: Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1.
    Author: Mohamed HS, Ibrahim ME, Miller EN, Peacock CS, Khalil EA, Cordell HJ, Howson JM, El Hassan AM, Bereir RE, Blackwell JM.
    Journal: Genes Immun; 2003 Jul; 4(5):351-5. PubMed ID: 12847550.
    Abstract:
    Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important. To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P=0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P=0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P=0.031) and associated (P=0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.
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