Identification of a novel G245R polymorphism in the IL-2 receptor β membrane proximal domain associated with human visceral leishmaniasis

被引:22
作者
Bucheton, B.
Argiro, L.
Chevillard, C.
Marquet, S.
Kheir, M. M.
Mergani, A.
El-Safi, S. H.
Dessein, A. J.
机构
[1] Fac Med La Timone, U399, INSERM, Marseille, France
[2] Univ Mediterranee, Fac Med La Timone, Lab Parasitol Mycol, Marseille, France
[3] Univ Khartoum, Fac Med, Dept Microbiol & Parasitol, Khartoum, Sudan
[4] Univ Gezira, Inst Nucl Med Mol Biol & Oncol, Wad Madani, Sudan
[5] Ctr IRD Montpellier, GEMI, UMR 2724, CNRS, F-34394 Montpellier 5, France
关键词
IL-2; receptor; IL2RB; Leishmaniasis; genetic association; human;
D O I
10.1038/sj.gene.6364355
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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- 2Rb). Present at a frequency of 7.2%, the IL-2-Rb 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.
引用
收藏
页码:79 / 83
页数:5
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