CD209 Genetic Polymorphism and Tuberculosis Disease
(2008) In PLoS ONE 3(1).- Abstract
- BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. METHODS AND FINDINGS: A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were... (More)
- BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. METHODS AND FINDINGS: A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2x2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. CONCLUSION: This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response. (Less)
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- author
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 3
- issue
- 1
- article number
- 1388
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:18167547
- scopus:38849171139
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0001388
- language
- English
- LU publication?
- no
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- 09c7a4dd-6d2b-46d7-9c8a-07773f13c516 (old id 1144259)
- date added to LUP
- 2016-04-01 14:47:52
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- 2022-01-28 02:31:26
@article{09c7a4dd-6d2b-46d7-9c8a-07773f13c516,
abstract = {{BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. METHODS AND FINDINGS: A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2x2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. CONCLUSION: This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response.}},
author = {{Vannberg, Fredrik O and Chapman, Stephen J and Khor, Chiea C and Tosh, Kerrie and Floyd, Sian and Jackson-Sillah, Dolly and Crampin, Amelia and Sichali, Lifted and Bah, Boubacar and Gustafson, Per and Aaby, Peter and McAdam, Keith P W J and Bah-Sow, Oumou and Lienhardt, Christian and Sirugo, Giorgio and Fine, Paul and Hill, Adrian V S}},
issn = {{1932-6203}},
language = {{eng}},
number = {{1}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{CD209 Genetic Polymorphism and Tuberculosis Disease}},
url = {{http://dx.doi.org/10.1371/journal.pone.0001388}},
doi = {{10.1371/journal.pone.0001388}},
volume = {{3}},
year = {{2008}},
}