title: Identification of a novel G245R polymorphism in the IL-2 receptor beta membrane proximal domain associated with human visceral leishmaniasis.
abstract: Binding of the interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferation and differentiation. We report here the identification of a novel G245R polymorphism in the membrane proximal domain of the IL-2 receptor beta chain (IL-2Rbeta). Present at a frequency of 7.2%, the IL-2-Rbeta G245R was identified in a population of Eastern Sudan exposed to a severe outbreak of visceral leishmaniasis (VL), a disease associated with a marked depression of T-cell antigen-specific responses. The location of the G245R polymorphism next to the box1/box2 proximal cytokine receptor homology segment and suggestive genetic association with the development of disease (P=0.043), suggest that it may affect Janus kinase (JAK) association and impair growth signal transduction. However, additional genetic association with a synonymous single nucleotide polymorphism (IL2RB+8777T) suggests that other variations of IL2RB or nearby genes participate in the highly significant linkage with VL at 22q12 previously reported for this population.
authors.affiliation: 1INSERM U399 Immunologie et Génétique des Maladies Parasitaires, Faculté de Médecine La Timone, Marseille, France. bucheton@mpl.ird.fr
authors.forename: B
authors.initials: B
authors.lastname: Bucheton
authors.forename: L
authors.initials: L
authors.lastname: Argiro
authors.forename: C
authors.initials: C
authors.lastname: Chevillard
authors.forename: S
authors.initials: S
authors.lastname: Marquet
authors.forename: M M
authors.initials: MM
authors.lastname: Kheir
authors.forename: A
authors.initials: A
authors.lastname: Mergani
authors.forename: S H
authors.initials: SH
authors.lastname: El-Safi
authors.forename: A J
authors.initials: AJ
authors.lastname: Dessein
mesh_terms: D019943:Amino Acid Substitution; D020022:Genetic Predisposition to Disease; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit / Q000737:chemistry / Q000235:genetics*; D053612:Janus Kinases / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013397:Sudan
chemical_list: D053646:Interleukin-2 Receptor beta Subunit; D053612:Janus Kinases