CD209 genetic polymorphism and tuberculosis disease.
<h4>Background</h4>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...
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Public Library of Science (PLoS)
2008-01-01
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| author | Fredrik O Vannberg Stephen J Chapman Chiea C Khor Kerrie Tosh Sian Floyd Dolly Jackson-Sillah Amelia Crampin Lifted Sichali Boubacar Bah Per Gustafson Peter Aaby Keith P W J McAdam Oumou Bah-Sow Christian Lienhardt Giorgio Sirugo Paul Fine Adrian V S Hill |
| author_facet | Fredrik O Vannberg Stephen J Chapman Chiea C Khor Kerrie Tosh Sian Floyd Dolly Jackson-Sillah Amelia Crampin Lifted Sichali Boubacar Bah Per Gustafson Peter Aaby Keith P W J McAdam Oumou Bah-Sow Christian Lienhardt Giorgio Sirugo Paul Fine Adrian V S Hill |
| author_sort | Fredrik O Vannberg |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods and findings</h4>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 2 x 2 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.<h4>Conclusion</h4>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. |
| format | Article |
| id | doaj-art-3bf431da418046018b6816ba4cdf67fc |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-3bf431da418046018b6816ba4cdf67fc2025-08-20T02:00:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0131e138810.1371/journal.pone.0001388CD209 genetic polymorphism and tuberculosis disease.Fredrik O VannbergStephen J ChapmanChiea C KhorKerrie ToshSian FloydDolly Jackson-SillahAmelia CrampinLifted SichaliBoubacar BahPer GustafsonPeter AabyKeith P W J McAdamOumou Bah-SowChristian LienhardtGiorgio SirugoPaul FineAdrian V S Hill<h4>Background</h4>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.<h4>Methods and findings</h4>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 2 x 2 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.<h4>Conclusion</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001388&type=printable |
| spellingShingle | Fredrik O Vannberg Stephen J Chapman Chiea C Khor Kerrie Tosh Sian Floyd Dolly Jackson-Sillah Amelia Crampin Lifted Sichali Boubacar Bah Per Gustafson Peter Aaby Keith P W J McAdam Oumou Bah-Sow Christian Lienhardt Giorgio Sirugo Paul Fine Adrian V S Hill CD209 genetic polymorphism and tuberculosis disease. PLoS ONE |
| title | CD209 genetic polymorphism and tuberculosis disease. |
| title_full | CD209 genetic polymorphism and tuberculosis disease. |
| title_fullStr | CD209 genetic polymorphism and tuberculosis disease. |
| title_full_unstemmed | CD209 genetic polymorphism and tuberculosis disease. |
| title_short | CD209 genetic polymorphism and tuberculosis disease. |
| title_sort | cd209 genetic polymorphism and tuberculosis disease |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001388&type=printable |
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