A gene providing protection against infectious diseases such as malaria and tuberculosis can also increase the risk of disease, an international team of researchers has discovered. The gene, which codes for a protein known as Mal, comes in two forms. People who inherit one copy of each form suffer less severe infections than those who inherit two copies of the same variant.

The Mal protein is part of the innate immune system, a non-specific defence system triggered by invading organisms. It was identified in 2001 by Professor Luke O'Neill from Trinity College Dublin, Ireland.

Now, Wellcome Fellow Professor Adrian Hill and his team have found that there are two common variants of the Mal gene, one highly active and one less reactive.

Working with patients in Kenya, The Gambia, Vietnam and the UK, the researchers found that having two copies of the overactive Mal gene doubled the risk of disease. In effect, the immune system goes into overdrive, actually worsening the symptoms of disease.

By contrast, with two copies of the less active form, the body does not fight the infection effectively.

However, with one copy of each variant, the immune system is more balanced, mounting a response but not damaging the body in the process.

The work suggests that drugs influencing this balance of Mal variants could reduce the likelihood of serious disease in those at risk.

The results of the study, funded by the Wellcome Trust, Science Foundation Ireland, Irish Health Research Board and the Agency for Science, Technology and Research (Singapore) are published in the April edition of Nature Genetics.

Image: Malaria Plasmodium falciparum

See also

• Press release (26 March)
• Major Overseas Programmes

External links

• Khor C et al. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nature Genetics 2007; [Epub ahead of print]
• Wellcome Trust Centre for Human Genetics