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

Genes & Immunity volume 4, pages 351–355 (2003)Cite this article

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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Acknowledgements

We thank the people of Sudan who contributed to this study. The work was supported by grants from the Wellcome Trust and the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR).

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Authors and Affiliations

  1. Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan

    H S Mohamed, M E Ibrahim, E A G Khalil, A M El Hassan & R E H Bereir

  2. Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK

    H S Mohamed, E N Miller, C S Peacock, H J Cordell, J M M Howson & J M Blackwell

Authors
  1. H S Mohamed
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  2. M E Ibrahim
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  3. E N Miller
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  4. C S Peacock
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  5. E A G Khalil
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  6. H J Cordell
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  7. J M M Howson
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  8. A M El Hassan
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  9. R E H Bereir
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  10. J M Blackwell
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Correspondence to J M Blackwell.

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Mohamed, H., Ibrahim, M., Miller, E. et al. Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1. Genes Immun 4, 351–355 (2003). https://doi.org/10.1038/sj.gene.6363977

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