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Lancet. 2003 May 31;361(9372):1871-2.

Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene.

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MRC Centre for Molecular and Cellular Biology and Department of Medical Biochemistry, Faculty of Health Sciences, Stellenbosch University, 7505, Tygerberg, South Africa.


Interferon gamma is believed to be crucial for host defence against many infections. To test the hypothesis that a polymorphism in the gene for interferon gamma (IFNG) is associated with susceptibility to tuberculosis, we did two independent investigations. In a case-control study of 313 tuberculosis cases, we noted a significant association between a polymorphism (+874A-->T) in IFNG and tuberculosis in a South African population (p=0.0055). This finding was replicated in a family-based study, in which the transmission disequilibrium test was used in 131 families (p=0.005). The transcription factor NFkappaB binds preferentially to the +874T allele, which is over-represented in controls. This preferential binding suggests that genetically determined variability in interferon gamma and expression might be important for the development of tuberculosis.

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