Heritability Analysis of Cytokines as Intermediate Phenotypes of Tuberculosis
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Date
2003
Journal Title
Journal ISSN
Volume Title
Publisher
The Journal of infectious diseases
Abstract
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)–g, tumor necrosis factor (TNF)–a, transforming growth factor (TGF)–b, 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-a, in particular,
had an estimated heritability of 68%. A principal component analysis of IFN-g, TNF-a, and TGF-b reflected
the immunologic model of TB. In this analysis, the first component explained 138% 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.
Description
Keywords
Heritability Analysis, Cytokines, Phenotypes, Tuberculosis
Citation
Stein, C. M., Guwatudde, D., Nakakeeto, M., Peters, P., Elston, R. C., Tiwari, H. K., ... & Whalen, C. C. (2003). Heritability analysis of cytokines as intermediate phenotypes of tuberculosis. The Journal of infectious diseases, 187(11), 1679-1685.