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Published on: July 15, 2011
IFNG +874 T>A single nucleotide polymorphism is associated with leprosy among Brazilians
C C Cardoso1, A C Pereira, V N Brito-de-Souza
1Laboratório de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ, Av Brasil 4365, Manguinhos, Rio de Janeiro CEP 21040-360, Brazil.
Human Genetics
|August 18, 2010
Summary
The IFNG gene
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Leprosy is a chronic infectious disease influenced by host genetics.
- The IFNG gene provides instructions for making interferon-gamma (IFN-γ), crucial for fighting intracellular pathogens.
- Single nucleotide polymorphisms (SNPs) in IFNG have been linked to infectious disease resistance.
Purpose of the Study:
- To investigate the association between the IFNG gene locus and leprosy in Brazilian populations.
- To evaluate specific SNPs within IFNG, including +874T>A (rs2430561), for their role in leprosy susceptibility or severity.
Main Methods:
- A case-control genetic epidemiological study involving 2,125 Brazilian subjects from São Paulo and 1,370 from Rio de Janeiro.
- Genotyping of IFNG SNPs: +874 T>A, +2109 A>G, and rs2069727.
- Analysis of spontaneous interferon-gamma release from peripheral blood mononuclear cells.
Main Results:
- The +874T allele of the IFNG gene showed a protective effect against leprosy (OR(adjusted) = 0.75; p = 0.005).
- This protective association was consistent across combined studies and supported by literature data.
- Higher spontaneous IFN-γ release was observed in +874T allele carriers, suggesting a functional immune response.
Conclusions:
- The IFNG +874T>A polymorphism plays a significant role in host resistance to mycobacterial diseases, including leprosy.
- The findings support the importance of host genetics in determining susceptibility and outcome of mycobacterial infections.
- The +874T allele may confer protection through enhanced interferon-gamma production.
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