A mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis Khor C. C. auteur aut IRD Chapman S. J. auteur aut IRD Vannberg F. O. auteur aut IRD Dunne A. auteur aut IRD Murphy C. auteur aut IRD Ling E. Y. auteur aut IRD Frodsham A. J. auteur aut IRD Walley A. J. auteur aut IRD Kyrieleis O. auteur aut IRD Khan A. auteur aut IRD Aucan C. auteur aut IRD Segal S. auteur aut IRD Moore C. E. auteur aut IRD Knox K. auteur aut IRD Campbell S. J. auteur aut IRD Lienhardt Christian auteur aut IRD Scott A. auteur aut IRD Aaby P. auteur aut IRD Sow O. Y. auteur aut IRD Grignani R. T. auteur aut IRD Sillah J. auteur aut IRD Sirugo G. auteur aut IRD Peshu N. auteur aut IRD Williams T. N. auteur aut IRD Maitland K. auteur aut IRD Davies R. J. O. auteur aut IRD Kwiatkowski D. P. auteur aut IRD Day N. P. auteur aut IRD Yala D. auteur aut IRD Crook D. W. auteur aut IRD Marsh K. auteur aut IRD Berkley J. A. auteur aut IRD O' Neill L.A.J. auteur aut IRD Hill A. V. S. auteur aut IRD text journalArticle eng Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens(1-3). The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction. specialized ALGERIE KENYA GAMBIE GUINEE GUINEE BISSAU VIET NAM ROYAUME UNI 020 052 Nature Genetics 39 4 523-528 2007 1061-4036 https://www.documentation.ird.fr/hor/fdi:010069206 10.1038/ng1976 1061-4036 [F B010069206] https://www.documentation.ird.fr/hor/fdi:010069206 IRD - Base Horizon / Pleins textes 2007-06-01 2017-08-23 fdi:010069206 fre