Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

H.S. Mohamed, M.E. Ibrahim, E.N. Miller, C.S. Peacock, E.A. Khalil, H.J. Cordell, J.M. Howson, A.M. El Hassan, R.E. Bereir, Jenefer Blackwell

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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.
Original languageEnglish
Pages (from-to)351-355
JournalGenes and Immunity
Volume4
Issue number5
DOIs
Publication statusPublished - 2003

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    Mohamed, H. S., Ibrahim, M. E., Miller, E. N., Peacock, C. S., Khalil, E. A., Cordell, H. J., Howson, J. M., El Hassan, A. M., Bereir, R. E., & Blackwell, J. (2003). Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1. Genes and Immunity, 4(5), 351-355. https://doi.org/10.1038/sj.gene.6363977