Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa.


Tosh, K; Campbell, SJ; Fielding, K; Sillah, J; Bah, B; Gustafson, P; Manneh, K; Lisse, I; Sirugo, G; Bennett, S; Aaby, P; McAdam, KP; Bah-Sow, O; Lienhardt, C; Kramnik, I; Hill, AV; (2006) Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa. Proceedings of the National Academy of Sciences of the United States of America, 103 (27). pp. 10364-8. ISSN 0027-8424 DOI: https://doi.org/10.1073/pnas.0603340103

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Abstract

The sst1 locus has been identified in a mouse model to control resistance and susceptibility of Mycobacterium tuberculosis infection. Subsequent studies have now identified Ipr1 (intracellular pathogen resistance 1) to be the gene responsible. Ipr1 is encoded within the sst1 locus and is expressed in the tuberculosis lung lesions and macrophages of sst1-resistant, but not sst1-susceptible mice. We have therefore examined the closest human homologue of Ipr1, SP110, for its ability to control susceptibility to M. tuberculosis infection in humans. In a study of families from The Gambia we have identified three polymorphisms that are associated with disease. On examination of additional families from Guinea-Bissau and the Republic of Guinea, two of these associations were independently replicated. These variants are in strong linkage disequilibrium with each other and lie within a 31-kb block of low haplotypic diversity, suggesting that a polymorphism within this region has a role in genetic susceptibility to tuberculosis in humans.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: TB Centre
Tropical Epidemiology Group
PubMed ID: 16803959
Web of Science ID: 239069400039
URI: http://researchonline.lshtm.ac.uk/id/eprint/11773

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