Vannberg, Fredrik O; Chapman, Stephen J; Khor, Chiea C; Tosh, Kerrie; Floyd, Sian; Jackson-Sillah, Dolly; Crampin, Amelia; Sichali, Lifted; Bah, Boubacar; Gustafson, Per; +7 more... Aaby, Peter; McAdam, Keith PWJ; Bah-Sow, Oumou; Lienhardt, Christian; Sirugo, Giorgio; Fine, Paul; Hill, Adrian VS; (2008) CD209 genetic polymorphism and tuberculosis disease. PloS one, 3 (1). e1388-. ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0001388
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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 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. 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 | Article |
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Faculty and Department |
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology & International Health (2023-) Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) |
Research Centre |
TB Centre Population Studies Group |
PubMed ID | 18167547 |
ISI | 260468900016 |
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