IFNG and IFNGR1 gene polymorphisms and susceptibility to post-kala-azar dermal leishmaniasis in Sudan.
Post-kala-azar dermal leishmanaisis (PKDL) in Sudan is associated with elevated interferon-gamma (IFN-gamma). To study interferon-gamma pathways in PKDL, we genotyped 80 trios from the Masalit ethnic group for polymorphisms at -470 ins/delTT, -270T/C, -56T/C and +95T/C in IFNGR1 and at -179G/A and +874T/A in IFNG. No associations occurred at IFNG. Global association with haplotypes comprising all four markers at IFNGR1 (chi(2)(10df)=21.97, P=0.015) was observed, associated with a significant (chi(2)(1df)=4.54, P=0.033) bias in transmission of the haplotype insTT T T T and less (chi(2)(1df)=5.59, P=0.018) than expected transmission of insTT C C C. When compared with data on malaria associations from Gambia, the results suggest a complex pattern of haplotypic variation at the IFNGR1 promoter locus associated with different infectious disease in African populations that reflect the complex roles of IFN-gamma in parasite killing versus inflammation and pathogenesis.
Salih
M A
MA
Institute of Endemic Disease, University of Khartoum, Khartoum, Sudan.
Ibrahim
M E
ME
Blackwell
J M
JM
Miller
E N
EN
Khalil
E A G
EA
ElHassan
A M
AM
Musa
A M
AM
Mohamed
H S
HS
D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000150:complications* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017471:Receptors, Interferon / Q000235:genetics*; D013397:Sudan; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor