Genetic control of visceral leishmaniasis in a Sudanese population: candidate gene testing indicates a linkage to the NRAMP1 region.
There is some evidence showing that genetic factors are involved in human susceptibility to parasitic diseases such as schistosomiasis and malaria. Studies have shown that the Nramp1 and H-2 genes are implicated in the control of Leishmania donovani infection in mice. We sought genetic loci involved in the control of susceptibility to visceral disease caused by L. donovani in humans. We studied 37 families with at least two affected sibs living in a village in eastern Sudan, where an outbreak of visceral leishmaniasis occurred between 1995 and 2000. The genetic markers located in five chromosomal regions containing candidate genes were typed: 2q35 (NRAMP1), 5q31-q33 (Th2 cytokine cluster), 6p21 (HLA/TNF-alpha), 6q23 (INFGRI) and 12q15 (INF-gamma). Linkage (multipoint lod-score=1.08; P=0.01) was observed for the 5'(CA) repeat polymorphism in the NRAMP1 promoter. This suggests that genetic variations of this gene affect susceptibility to visceral leishmaniasis in this population.
Bucheton
B
B
Genétique et Immunologie des Maladies Parasities, INSERM U399, Faculté de Médicine de La Timone, Marseille, France.
Abel
L
L
Kheir
M M
MM
Mirgani
A
A
El-Safi
S H
SH
Chevillard
C
C
Dessein
A
A
D000293:Adolescent; D000328:Adult; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D013397:Sudan; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D005819:Genetic Markers; D000099173:Natural Resistance-associated Macrophage Protein 1