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

Tosh, Kerrie ; Campbell, Sarah J ; Fielding, Katherine ; Sillah, Jackson ; Bah, Boubacar ; Gustafson, Per LU ; Manneh, Kebba ; Lisse, Ida ; Sirugo, Giorgio and Bennett, Steve , et al. (2006) In Proceedings of the National Academy of Sciences 103(27). p.10364-10368
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,... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
103
issue
27
pages
10364 - 10368
publisher
National Academy of Sciences
external identifiers
  • pmid:16803959
  • scopus:33745897329
  • pmid:16803959
ISSN
1091-6490
DOI
10.1073/pnas.0603340103
language
English
LU publication?
yes
id
3a2ea66b-c951-4254-96f0-7bc49ec6639a (old id 1135623)
date added to LUP
2016-04-01 12:34:24
date last changed
2022-01-27 06:55:14
@article{3a2ea66b-c951-4254-96f0-7bc49ec6639a,
  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.}},
  author       = {{Tosh, Kerrie and Campbell, Sarah J and Fielding, Katherine and Sillah, Jackson and Bah, Boubacar and Gustafson, Per and Manneh, Kebba and Lisse, Ida and Sirugo, Giorgio and Bennett, Steve and Aaby, Peter and McAdam, Keith P W J and Bah-Sow, Oumou and Lienhardt, Christian and Kramnik, Ig}},
  issn         = {{1091-6490}},
  language     = {{eng}},
  number       = {{27}},
  pages        = {{10364--10368}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences}},
  title        = {{Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa}},
  url          = {{http://dx.doi.org/10.1073/pnas.0603340103}},
  doi          = {{10.1073/pnas.0603340103}},
  volume       = {{103}},
  year         = {{2006}},
}