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Am J Trop Med Hyg. 2013 Jul;89(1):169-73. doi: 10.4269/ajtmh.12-0670. Epub 2013 Apr 29.

Genetic and shared environmental influences on interferon-γ production in response to Mycobacterium tuberculosis antigens in a Ugandan population.

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Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.


Interferon-γ (IFN-γ) is a key cytokine in the immune response to Mycobacterium tuberculosis (Mtb). Many studies established IFN-γ responses are influenced by host genetics, however differed widely by the study design and heritability estimation method. We estimated heritability of IFN-γ responses to Mtb culture filtrate (CF), ESAT-6, and Antigen 85B (Ag85B) in 1,104 Ugandans from a household contact study. Our method separately evaluates shared environmental and genetic variance, therefore heritability estimates were not upwardly biased, ranging from 11.6% for Ag85B to 22.9% for CF. Subset analyses of individuals with latent Mtb infection or without human immunodeficiency virus infection yielded higher heritability estimates, suggesting 10-30% of variation in IFN-γ is caused by a shared environment. Immunosuppression does not negate the role of genetics on IFN-γ response. These estimates are remarkably close to those reported for components of the innate immune response. These findings have implications for the interpretation of IFN-γ response assays and vaccine studies.

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