Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1.
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.
Mohamed
H S
HS
Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Ibrahim
M E
ME
Miller
E N
EN
Peacock
C S
CS
Khalil
E A G
EA
Cordell
H J
HJ
Howson
J M M
JM
El Hassan
A M
AM
Bereir
R E H
RE
Blackwell
J M
JM
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
D015847:Interleukin-4; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor