Three Human Gene Variants Appear To Influence Tuberculosis Susceptibility

Approximately one-third of the world's population is thought to be infected with the M. tuberculosis pathogen, yet only about 10 percent becomes ill with the active disease. Researchers suspect that a variety of factors interplay to determine who develops the full-blown disease. For example, in February 2006 Harvard School of Public Health (HSPH) researchers were part of a team that identified a mechanism that explains why people of African descent may be more vulnerable to the disease.

Now HSPH Associate Professor Igor Kramnik is part of a team led by Professor Adrian V.S. Hill of Oxford University that has identified three variations of a human gene associated with tuberculosis susceptibility. The lead author on the paper is Kerrie Tosh of the Wellcome Trust Centre for Human Genetics in the U.K.

Kramnik and his colleagues had previously identified a gene in mice called Ipr1 (intracellular pathogen resistance 1) that plays a significant role in limiting the multiplication of intracellular pathogens M. tuberculosis and Listeria monocytogenes inside host cells.

The Hill team then examined the closest homolog of the mouse gene Ipr1 that can be found in humans--a gene called SP110. Three variations of the SP110 gene were found to be associated with tuberculosis in humans.

The variations of SP110 emerged from an analysis of 20 pieces of genetic material called SNPs that were culled from an original set of 27 SNPs taken from samples provided by 219 families in The Gambia. Two of the variations and their association with tuberculosis were further replicated in samples from 99 families in the Republic of Guinea and 102 families in Guinea-Bissau.

This study was supported by funds from the European Commission, Wellcome Trust, National Institutes of Health, and Medical Research Council.