June 5, 2003 Access past issues

Reviewed by: Snehal S. Ruparelia Office of Genomics and Disease Prevention

The Health Outcome

Tuberculosis (TB) is a mycobacterial disease that is an important cause of death and disability in many parts of the world. It is caused by Mycobacterium tuberculosis, a slender, rod-shaped bacterium which most commonly attacks the lungs (pulmonary TB) but also can infect other parts of the body (extrapulmonary TB).(1)An estimated one-third of the world’s population is infected with the pathogen but only 10% develop clinical disease. In industrialized countries, mortality and morbidity decreased until the late 1980s after which there was an increased prevalence among certain populations including those who have with a high prevalence of HIV infection and who live in areas where TB is endemic. In the United States, TB disease has declined since 1994.  Typically, death and morbidity rates increase with age and are higher for males than for females. Latent infection (detected by a positive tuberculin skin-test) results in no symptoms, whereas clinical disease is characterized by weight loss, fever, chest pain, and coughing.(2)

The Finding

Awomoyi et al. performed two case-control studies in a population of males from two clinical settings in The Gambia to elucidate the association between the SLC11A1 polymorphism and TB susceptibility as well as to investigate the role of this polymorphism in innate macrophage responses to mycobacterial infection.  In the first case-control study, the researchers found an increase in anti-inflammatory Interleukin-10 production among persons with Allele 2 of the polymorphism (this allele is associated with susceptibility to TB) resulting from decreased production of Interferon (IFN)-3

Public Health Implications

This study demonstrates a dose-response relation between susceptibility to TB infection and increased production of IL-10 in people with allele 2 of the polymorphism. Manipulation of the IL-10 pathway that would maintain a balance between the pro- and anti-inflammatory effects within cells should be further investigated as therapy for mycobacterial infection. However, the frequency of allele 2 is relatively lower (0.25) than its resistant counterpart (allele 3 with a frequency of 0.75).  SLC11A1 gene.  Only after more research can the public health implications of this polymorphism be defined.

References

1. Centers for Disease Control and Prevention.  Health Topics:  Tuberculosis.  Atlanta:  Centers for Disease Control and Prevention; 2002
2. Chin,J.  Tuberculosis.  Control of Communicable Diseases Manual 17 Edition 2000.  521-530.
3. Awomoyi AA, Marchant A, Howson JM. et al. Interluekin-10 Polymorphism in SLC11A1 (formerly NRAMP1), and Susceptibility to Tuberculosis. J Inf Dis 2002 186:1808-14.