苏丹IFNG和IFNGR1基因多态性与黑热病后皮肤利什曼病易感性
IFNG and IFNGR1 gene polymorphisms and susceptibility to post-kala-azar dermal leishmaniasis in Sudan.
作者信息
Salih M A, Ibrahim M E, Blackwell J M, Miller E N, Khalil E A G, ElHassan A M, Musa A M, Mohamed H S
机构信息
Institute of Endemic Disease, University of Khartoum, Khartoum, Sudan.
出版信息
Genes Immun. 2007 Jan;8(1):75-8. doi: 10.1038/sj.gene.6364353. Epub 2006 Nov 30.
Abstract
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.
摘要
苏丹的黑热病后皮肤利什曼病（PKDL）与干扰素-γ（IFN-γ）水平升高有关。为了研究PKDL中的干扰素-γ通路，我们对来自马萨利特族的80个三联体进行基因分型，检测IFNGR1基因中-470 ins/delTT、-270T/C、-56T/C和+95T/C位点以及IFNG基因中-179G/A和+874T/A位点的多态性。在IFNG基因未发现关联。观察到与IFNGR1基因包含所有四个标记的单倍型存在总体关联（χ²(10自由度)=21.97，P=0.015），其中单倍型insTT T T T的传递存在显著偏差（χ²(1自由度)=4.54，P=0.033），而单倍型insTT C C C的传递低于预期（χ²(1自由度)=5.59，P=0.018）。与来自冈比亚的疟疾关联数据相比，结果表明IFNGR1启动子位点存在复杂的单倍型变异模式，这与非洲人群中不同的传染病相关，反映了IFN-γ在杀灭寄生虫与炎症及发病机制中的复杂作用。
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