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Polymorphism within the interferon-gamma/receptor complex is associated with pulmonary tuberculosis

Cooke, Graham S ; Campbell, Sarah J ; Sillah, Jackson ; Gustafson, Per LU ; Bah, Boubacar ; Sirugo, Georgio ; Bennett, Steve ; McAdam, Keith P W J ; Sow, Oumou and Lienhardt, Christian , et al. (2006) In American Journal of Respiratory and Critical Care Medicine 174(3). p.339-343
Abstract
RATIONALE: Interferon-gamma (IFN-gamma) is of central interest in the study of tuberculosis. A number of single-gene mutations have been identified in the IFN-gamma signaling pathway that predispose to severe mycobacterial disease, but the relevance of polymorphism within these genes to the common phenotype of tuberculosis remains unclear. METHODS: A total of 1,301 individuals were included in a large, detailed study of West African populations with pulmonary tuberculosis. We investigated disease association with the genes encoding IFN-gamma and its receptor subunits (IFNG, IFNGR1, and IFNGR2). RESULTS: Within the IFNG gene, two promoter variants showed evidence of novel disease association: -1616GG (odds ratio [OR], 1.49; 95% confidence... (More)
RATIONALE: Interferon-gamma (IFN-gamma) is of central interest in the study of tuberculosis. A number of single-gene mutations have been identified in the IFN-gamma signaling pathway that predispose to severe mycobacterial disease, but the relevance of polymorphism within these genes to the common phenotype of tuberculosis remains unclear. METHODS: A total of 1,301 individuals were included in a large, detailed study of West African populations with pulmonary tuberculosis. We investigated disease association with the genes encoding IFN-gamma and its receptor subunits (IFNG, IFNGR1, and IFNGR2). RESULTS: Within the IFNG gene, two promoter variants showed evidence of novel disease association: -1616GG (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.11-2.00; p = 0.008) and +3234TT (OR, 1.40; 95% CI, 1.09-1.80; p = 0.009). The +874AA genotype was not significantly more frequent among cases over control subjects (OR, 1.16; 95%CI, 0.89-1.51; p = 0.25). In addition, novel disease association was also found with the -56CC genotype of the IFNGR1 promoter (OR, 0.75; 95% CI, 0.57-0.99; p = 0.041). No disease association was seen with the IFNGR2 locus. CONCLUSIONS: These results provide evidence of a significant role for genetic variation at the IFNG locus and provide detailed understanding of the genetic mechanisms underlying this association. The disease association with IFNGR1 is novel, and together these findings support the hypothesis that genetically determined variation in both IFN-gamma production and responsiveness influences the risk of developing tuberculosis. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
receptor, interferon-gamma, polymorphism, tuberculosis
in
American Journal of Respiratory and Critical Care Medicine
volume
174
issue
3
pages
339 - 343
publisher
American Thoracic Society
external identifiers
  • pmid:16690980
  • scopus:33746615072
ISSN
1535-4970
DOI
10.1164/rccm.200601-088OC
language
English
LU publication?
yes
id
71a80621-a663-4f52-b8cc-a04ba2d45766 (old id 1135603)
date added to LUP
2016-04-01 11:50:42
date last changed
2021-10-10 04:57:15
@article{71a80621-a663-4f52-b8cc-a04ba2d45766,
  abstract     = {RATIONALE: Interferon-gamma (IFN-gamma) is of central interest in the study of tuberculosis. A number of single-gene mutations have been identified in the IFN-gamma signaling pathway that predispose to severe mycobacterial disease, but the relevance of polymorphism within these genes to the common phenotype of tuberculosis remains unclear. METHODS: A total of 1,301 individuals were included in a large, detailed study of West African populations with pulmonary tuberculosis. We investigated disease association with the genes encoding IFN-gamma and its receptor subunits (IFNG, IFNGR1, and IFNGR2). RESULTS: Within the IFNG gene, two promoter variants showed evidence of novel disease association: -1616GG (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.11-2.00; p = 0.008) and +3234TT (OR, 1.40; 95% CI, 1.09-1.80; p = 0.009). The +874AA genotype was not significantly more frequent among cases over control subjects (OR, 1.16; 95%CI, 0.89-1.51; p = 0.25). In addition, novel disease association was also found with the -56CC genotype of the IFNGR1 promoter (OR, 0.75; 95% CI, 0.57-0.99; p = 0.041). No disease association was seen with the IFNGR2 locus. CONCLUSIONS: These results provide evidence of a significant role for genetic variation at the IFNG locus and provide detailed understanding of the genetic mechanisms underlying this association. The disease association with IFNGR1 is novel, and together these findings support the hypothesis that genetically determined variation in both IFN-gamma production and responsiveness influences the risk of developing tuberculosis.},
  author       = {Cooke, Graham S and Campbell, Sarah J and Sillah, Jackson and Gustafson, Per and Bah, Boubacar and Sirugo, Georgio and Bennett, Steve and McAdam, Keith P W J and Sow, Oumou and Lienhardt, Christian and Hill, Adrian V S},
  issn         = {1535-4970},
  language     = {eng},
  number       = {3},
  pages        = {339--343},
  publisher    = {American Thoracic Society},
  series       = {American Journal of Respiratory and Critical Care Medicine},
  title        = {Polymorphism within the interferon-gamma/receptor complex is associated with pulmonary tuberculosis},
  url          = {http://dx.doi.org/10.1164/rccm.200601-088OC},
  doi          = {10.1164/rccm.200601-088OC},
  volume       = {174},
  year         = {2006},
}