CD209 genetic polymorphism and tuberculosis disease

Vannberg, F. O. et al. (2008) CD209 genetic polymorphism and tuberculosis disease. PLoS ONE, 3(1), e1388. (doi: 10.1371/journal.pone.0001388) (PMID:18167547) (PMCID:PMC2148105)

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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 χ2 = 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 2×2 χ2 = 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.

Item Type:Articles
Additional Information:Funding: The tuberculosis samples were collected as part of an EU-funded project (contract number IC18CT980375). This work was funded by the Wellcome Trust.
Glasgow Author(s) Enlighten ID:Crampin, Professor Mia
Authors: Vannberg, F. O., Chapman, S. J., Khor, C. C., Tosh, K., Floyd, S., Jackson-Sillah, D., Crampin, A., Sichali, L., Bah, B., Gustafson, P., Aaby, P., McAdam, K. P. W. J., Bah-Sow, O., Lienhardt, C., Sirugo, G., Fine, P., and Hill, A. V. S.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2008 Vannberg et al.
First Published:First published in PLoS ONE 3(1):e1388
Publisher Policy:Reproduced under a Creative Commons license

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