细胞因子作为结核病中间表型的遗传力分析。
Heritability analysis of cytokines as intermediate phenotypes of tuberculosis.
作者信息
Stein Catherine M, Guwatudde David, Nakakeeto Margaret, Peters Pierre, Elston Robert C, Tiwari Hemant K, Mugerwa Roy, Whalen Christopher C
机构信息
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
出版信息
J Infect Dis. 2003 Jun 1;187(11):1679-85. doi: 10.1086/375249. Epub 2003 May 9.
Numerous studies have provided support for genetic susceptibility to tuberculosis (TB); however, heterogeneity in disease expression has hampered previous genetic studies. The purpose of this work was to investigate possible intermediate phenotypes for TB. A set of cytokine profiles, including antigen-stimulated whole-blood assays for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and the ratio of IFN to TNF, were analyzed in 177 pedigrees from a community in Uganda with a high prevalence of TB. The heritability of these variables was estimated after adjustment for covariates, and TNF-alpha, in particular, had an estimated heritability of 68%. A principal component analysis of IFN-gamma, TNF-alpha, and TGF-beta reflected the immunologic model of TB. In this analysis, the first component explained >38% of the variation in the data. This analysis illustrates the value of such intermediate phenotypes in mapping susceptibility loci for TB and demonstrates that this area deserves further research.
众多研究为结核病（TB）的遗传易感性提供了支持；然而，疾病表现的异质性阻碍了先前的遗传学研究。这项工作的目的是研究结核病可能的中间表型。对乌干达一个结核病高流行社区的177个家系进行了一组细胞因子谱分析，包括抗原刺激全血检测干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β以及IFN与TNF的比值。在对协变量进行调整后估计了这些变量的遗传力，特别是TNF-α的估计遗传力为68%。对IFN-γ、TNF-α和TGF-β进行主成分分析反映了结核病的免疫模型。在此分析中，第一成分解释了数据中>38%的变异。该分析说明了此类中间表型在绘制结核病易感基因座中的价值，并表明该领域值得进一步研究。
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