Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene.
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.
Rossouw
Manda
M
MRC Centre for Molecular and Cellular Biology and Department of Medical Biochemistry, Faculty of Health Sciences, Stellenbosch University, 7505, Tygerberg, South Africa.
Nel
Hendrik J
HJ
Cooke
Graham S
GS
van Helden
Paul D
PD
Hoal
Eileen G
EG
D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013019:South Africa; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology
D016898:Interferon-alpha; D016328:NF-kappa B