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 CD209-33CA/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 2×2 X2 = 7.47, P=0.006, odds ratio = 0.86,95%Cl 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 X2 = 17.34, P=0.03003, odds ratio = 0.42, 95%Cl 0.27-0.63). 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. © 2008 Vannberg et al.
CITATION STYLE
Vannberg, F. O., Chapman, S. J., Khor, C. C., Tosh, K., Floyd, S., Jackson-Sillah, D., … Hill, A. V. S. (2008). CD209 genetic polymorphism and tuberculosis disease. PLoS ONE, 3(1). https://doi.org/10.1371/journal.pone.0001388
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