title: Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1.
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.
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: H S
authors.initials: HS
authors.lastname: Mohamed
authors.forename: M E
authors.initials: ME
authors.lastname: Ibrahim
authors.forename: E N
authors.initials: EN
authors.lastname: Miller
authors.forename: C S
authors.initials: CS
authors.lastname: Peacock
authors.forename: E A G
authors.initials: EA
authors.lastname: Khalil
authors.forename: H J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: J M M
authors.initials: JM
authors.lastname: Howson
authors.forename: A M
authors.initials: AM
authors.lastname: El Hassan
authors.forename: R E H
authors.initials: RE
authors.lastname: Bereir
authors.forename: J M
authors.initials: JM
authors.lastname: Blackwell
mesh_terms: D000483:Alleles; D000704:Analysis of Variance; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000235:genetics* / Q000276:immunology; D016013:Likelihood Functions; D016015:Logistic Models; D011110:Polymorphism, Genetic; D017471:Receptors, Interferon / Q000235:genetics* / Q000276:immunology; D013397:Sudan; D000096743:Interferon gamma Receptor
chemical_list: D015847:Interleukin-4; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor