Abstract
CD1 proteins are antigen-presenting molecules that evolved to present lipids rather than peptides to T cells. However, unlike major histocompatibility complex genes, CD1 genes show low rates of polymorphism and have not been clearly associated with human disease. We report that an intronic polymorphism in CD1A (rs411089) is associated with susceptibility to tuberculosis in two cohorts of Vietnamese adults (combined cohort odds ratio 1.78; 95% confidence interval: 1.24–2.57; P=0.001). These data strengthen the hypothesis that CD1A-mediated lipid antigen presentation is important for controlling tuberculosis in humans.
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Acknowledgements
We acknowledge the work of the clinical staff from the Hospital of Tropical Diseases and Pham Ngoc Thach Hospital who initially diagnosed and studied the patients with TBM and PTB. We thank Dr Nguyen Thi Hieu from the Hung Vuong Obstetric Hospital, Vietnam, Dr Tran Tinh Hien from the Hospital for Tropical Diseases, Vietnam and all the Vietnamese doctors and patients who participated in this study. We thank Dr Alan Aderem (Seattle BioMed), Dr Marta Janer and Dr Sarah Li (Institute for Systems Biology) for advice and technical assistance. This study was funded in part by the NIH (K24AI089794 to TRH and K08AI089938 to CS), the Burroughs Wellcome Foundation (TRH) and the Irvington Institute Fellowship Program (CS). The clinical component of this study was funded through the Wellcome Trust Major Overseas Program in Vietnam (089276/Z/09/Z).
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The findings described here are unpublished but were presented as an oral abstract at the Sixth International Symposium on CD1 and NKT Cells (Chicago, IL, USA, 23–27 September 2011) and as a poster at the Host Response in Tuberculosis Keystone Symposium (Whistler, CA, USA, 13–18 March 2013).
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Seshadri, C., Thuong, N., Yen, N. et al. A polymorphism in human CD1A is associated with susceptibility to tuberculosis. Genes Immun 15, 195–198 (2014). https://doi.org/10.1038/gene.2014.5
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DOI: https://doi.org/10.1038/gene.2014.5
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