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|Title:||Anassociation study of TOLL and CARD with leprosy susceptibility in Chinese population||Authors:||Liu, H.
|Issue Date:||Nov-2013||Citation:||Liu, H., Bao, F., Irwanto, A., Fu, X., Lu, N., Yu, G., Yu, Y., Sun, Y., Low, H., Li, Y., Liany, H., Yuan, C., Li, J., Liu, J., Chen, M., Liu, H., Wang, N., You, J., Ma, S., Niu, G., Zhou, Y., Chu, T., Tian, H., Chen, S., Zhang, X., Liu, J., Zhang, F. (2013-11). Anassociation study of TOLL and CARD with leprosy susceptibility in Chinese population. Human Molecular Genetics 22 (21) : 4430-4437. ScholarBank@NUS Repository. https://doi.org/10.1093/hmg/ddt286||Abstract:||Previousgenome-wideassociationstudies (GWASs)identifiedmultiple susceptibility loci thathavehighlighted the important role of TLR (Toll-like receptor) and CARD (caspase recruitment domain) genes in leprosy. A large threestagecandidategene- basedassociationstudy of30TLRand47CARDgeneswasperformedintheleprosysamples of ChineseHan. Of 4363SNPs investigated, eight SNPs showed suggestive association (P < 0.01) in our previously published GWAS datasets (Stage 1). Of the eight SNPs, rs2735591 and rs4889841 showed significant association (P < 0.001) in an independent series of 1504 cases and 1502 controls (Stage 2), but only rs2735591 (next to BCL10) showed significant association in the second independent series of 938 cases and 5827 controls (Stage 3). Rs2735591 showed consistent association across the three stages (P > 0.05 for heterogeneity test), significant association in the combined validation samples (Pcorrected 5 5.54 3 10-4 after correction for 4363 SNPs tested) and genome-widesignificanceinthewholeGWASandvalidationsamples(P 5 1.03 3 10-9, OR 5 1.24). Inaddition, we demonstrated the lower expression of BCL10 in leprosy lesions than normal skins and a significant gene connectionbetweenBCL10and theeightpreviously identifiedleprosy loci that areassociated withNFkB, amajor regulator of downstreaminflammatory responses, which provides further biological evidence for the association. We have discovered a novel susceptibility locus on 1p22,which implicates BCL10 as a new susceptibility gene for leprosy. Our finding highlights the important role of both innate and adaptive immune responses in leprosy. © The Author 2013. Published by Oxford University Press. All rights reserved.||Source Title:||Human Molecular Genetics||URI:||http://scholarbank.nus.edu.sg/handle/10635/108869||ISSN:||09646906||DOI:||10.1093/hmg/ddt286|
|Appears in Collections:||Staff Publications|
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