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Variants of the CD40 ligand gene are not associated with increased susceptibility to tuberculosis in West Africa

Campbell, Sarah J; Sabeti, Pardis; Fielding, Katherine; Sillah, Jackson; Bah, Boubacar; Gustafson, Per LU ; Manneh, Kebba; Lisse, Ida; Sirugo, Giorgio and Bellamy, Richard, et al. (2003) In Immunogenetics 55(7). p.502-507
Abstract
Evidence for linkage between tuberculosis and human chromosomal region Xq26 has previously been described. The costimulatory molecule CD40 ligand, encoded by TNFSF5 and located at Xq26.3, is a promising positional candidate. Interactions between CD40 ligand and CD40 are involved in the development of humoral- and cell-mediated immunity, as well as the activation of macrophages, which are the primary host and effector cells for Mycobacterium tuberculosis. We hypothesised that common variation within TNFSF5 might affect susceptibility to tuberculosis disease and, thus, might be responsible for the observed linkage to Xq26. Sequencing 32 chromosomes from a Gambian population identified nine common polymorphisms within the coding, 3' and 5'... (More)
Evidence for linkage between tuberculosis and human chromosomal region Xq26 has previously been described. The costimulatory molecule CD40 ligand, encoded by TNFSF5 and located at Xq26.3, is a promising positional candidate. Interactions between CD40 ligand and CD40 are involved in the development of humoral- and cell-mediated immunity, as well as the activation of macrophages, which are the primary host and effector cells for Mycobacterium tuberculosis. We hypothesised that common variation within TNFSF5 might affect susceptibility to tuberculosis disease and, thus, might be responsible for the observed linkage to Xq26. Sequencing 32 chromosomes from a Gambian population identified nine common polymorphisms within the coding, 3' and 5' regulatory sequences of the gene. Six single nucleotide polymorphisms (SNPs) and a 3' microsatellite were genotyped in 121 tuberculosis patients and their available parents. No association with tuberculosis was detected for these variants using a transmission disequilibrium test, although one SNP at -726 showed some evidence of association in males. This finding, however, did not replicate in a separate case control study of over 1,200 West African individuals. We conclude that common genetic variation in TNFSF5 is not likely to affect tuberculosis susceptibility in West Africa and the linkage observed in this region is not due to variation in TNFSF5. (Less)
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publication status
published
subject
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Immunogenetics
volume
55
issue
7
pages
502 - 507
publisher
Springer
external identifiers
  • pmid:12955358
  • scopus:0242551851
ISSN
1432-1211
DOI
10.1007/s00251-003-0602-9
language
English
LU publication?
no
id
3e01adfe-79dd-4cc2-9735-034be993ff4b (old id 1126715)
date added to LUP
2008-06-02 15:23:55
date last changed
2018-05-29 11:26:38
@article{3e01adfe-79dd-4cc2-9735-034be993ff4b,
  abstract     = {Evidence for linkage between tuberculosis and human chromosomal region Xq26 has previously been described. The costimulatory molecule CD40 ligand, encoded by TNFSF5 and located at Xq26.3, is a promising positional candidate. Interactions between CD40 ligand and CD40 are involved in the development of humoral- and cell-mediated immunity, as well as the activation of macrophages, which are the primary host and effector cells for Mycobacterium tuberculosis. We hypothesised that common variation within TNFSF5 might affect susceptibility to tuberculosis disease and, thus, might be responsible for the observed linkage to Xq26. Sequencing 32 chromosomes from a Gambian population identified nine common polymorphisms within the coding, 3' and 5' regulatory sequences of the gene. Six single nucleotide polymorphisms (SNPs) and a 3' microsatellite were genotyped in 121 tuberculosis patients and their available parents. No association with tuberculosis was detected for these variants using a transmission disequilibrium test, although one SNP at -726 showed some evidence of association in males. This finding, however, did not replicate in a separate case control study of over 1,200 West African individuals. We conclude that common genetic variation in TNFSF5 is not likely to affect tuberculosis susceptibility in West Africa and the linkage observed in this region is not due to variation in TNFSF5.},
  author       = {Campbell, Sarah J and Sabeti, Pardis and Fielding, Katherine and Sillah, Jackson and Bah, Boubacar and Gustafson, Per and Manneh, Kebba and Lisse, Ida and Sirugo, Giorgio and Bellamy, Richard and Bennett, Steve and Aaby, Peter and McAdam, Keith P W J and Bah-Sow, Oumou and Lienhardt, Ch},
  issn         = {1432-1211},
  language     = {eng},
  number       = {7},
  pages        = {502--507},
  publisher    = {Springer},
  series       = {Immunogenetics},
  title        = {Variants of the CD40 ligand gene are not associated with increased susceptibility to tuberculosis in West Africa},
  url          = {http://dx.doi.org/10.1007/s00251-003-0602-9},
  volume       = {55},
  year         = {2003},
}