Promoter variation in the DC-SIGN–Encoding Gene CD209 is associated with tuberculosis
Date
2006-01
Authors
Barreiro, Luis B.
Neyrolles, Olivier
Babb, Chantal L.
Tailleux, Ludovic
Quach, Helene
McElreavey, Ken
Van Helden, Paul D.
Hoal, Eileen G.
Gicquel, Brigitte
Quintana-Murci, Lluis
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science (PLOS)
Abstract
Background
Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading
causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M.
tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M.
tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of
influence in the pathogenesis of a number of infectious diseases, including tuberculosis.
Methods and Findings
We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated
with susceptibility to tuberculosis through sequencing and genotyping analyses in a South
African cohort. After exclusion of significant population stratification in our cohort, we
observed an association between two CD209 promoter variants ( 871G and 336A) and
decreased risk of developing tuberculosis. By looking at the geographical distribution of these
variants, we observed that their allelic combination is mainly confined to Eurasian populations.
Conclusions
Our observations suggest that the two 871G and 336A variants confer protection against
tuberculosis. In addition, the geographic distribution of these two alleles, together with their
phylogenetic status, suggest that they may have increased in frequency in non-African
populations as a result of host genetic adaptation to a longer history of exposure to
tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in
tuberculosis will be crucial to better appreciate the role of this lectin in interactions between
the host immune system and the tubercle bacillus as well as other pathogens.
Description
The original publication is available at http://www.plosmedicine.org
Keywords
Mycobacterium tuberculosis, C-type lectin DC-SIGN
Citation
Barreiro, L. B. et al 2006. Promoter variation in the DCSIGN– encoding gene CD209 is associated with tuberculosis. PLoS Med, 3(2), e20, doi:10.1371/journal.pmed.0030020.