title: A major susceptibility locus on chromosome 22q12 plays a critical role in the control of kala-azar.
abstract: Kala-azar (KA) is a life-threatening protozoal disease caused by Leishmania parasites (L. donovani, L. chagasi, and L. infantum). The disease, which is also called "visceral leishmaniasis," is prevalent in Africa, South America, Asia, and the Mediterranean basin. Epidemics occur periodically, killing a large number of infected individuals. Factors determining whether a patient remains asymptomatic or develops KA are still largely unknown. In a previous study that was performed during an outbreak of KA in a village on the Ethiopian-Sudanese border, we showed that KA was more frequent in certain families and ethnic groups, thereby suggesting that host genetic factors play an important role in the development of the disease. Here, we report the results of a genomewide linkage study performed on 63 Sudanese families selected from the most affected ethnic group and including 169 children with KA. Significant linkage (LOD score 3.50 [P=3x10-5] in all patients; LOD score 3.90 [P=10-5] in patients who were affected early in the outbreak) was obtained with markers on chromosome 22q12. These results are the first evidence of a major genetic effect on the development of human KA. They may lead to identification of genes critical in the pathogenesis of this disease and to new therapeutic interventions against this parasite, which is developing resistance to available drugs.
authors.affiliation: INSERM U399, Immunology and Genetics of Parasitic Diseases, Faculté de Médecine La Timone, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bucheton
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Sayda
authors.initials: S
authors.lastname: El-Safi
authors.forename: Musa M
authors.initials: MM
authors.lastname: Kheir
authors.forename: Sylvana
authors.initials: S
authors.lastname: Pavek
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lemainque
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Dessein
mesh_terms: D000328:Adult; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004196:Disease Outbreaks; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000235:genetics*; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D035781:Siblings; D013397:Sudan / Q000453:epidemiology