Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0072037
Title: Replication and Meta-Analysis of GWAS Identified Susceptibility Loci in Kawasaki Disease Confirm the Importance of B Lymphoid Tyrosine Kinase (BLK) in Disease Susceptibility
Authors: Chang, C.-J.
Kuo, H.-C.
Chang, J.-S.
Lee, J.-K.
Tsai, F.-J.
Khor, C.C. 
Chang, L.-C.
Chen, S.-P.
Ko, T.-M.
Liu, Y.-M.
Chen, Y.-J.
Hong, Y.M.
Jang, G.Y.
Hibberd, M.L.
Kuijpers, T.
Burgner, D.
Levin, M.
Burns, J.C.
Davila, S.
Chen, Y.-T.
Chen, C.-H.
Wu, J.-Y.
Lee, Y.-C.
Issue Date: 30-Aug-2013
Citation: Chang, C.-J., Kuo, H.-C., Chang, J.-S., Lee, J.-K., Tsai, F.-J., Khor, C.C., Chang, L.-C., Chen, S.-P., Ko, T.-M., Liu, Y.-M., Chen, Y.-J., Hong, Y.M., Jang, G.Y., Hibberd, M.L., Kuijpers, T., Burgner, D., Levin, M., Burns, J.C., Davila, S., Chen, Y.-T., Chen, C.-H., Wu, J.-Y., Lee, Y.-C. (2013-08-30). Replication and Meta-Analysis of GWAS Identified Susceptibility Loci in Kawasaki Disease Confirm the Importance of B Lymphoid Tyrosine Kinase (BLK) in Disease Susceptibility. PLoS ONE 8 (8) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0072037
Abstract: The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10-31). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD. © 2013 Chang et al.
Source Title: PLoS ONE
URI: http://scholarbank.nus.edu.sg/handle/10635/108796
ISSN: 19326203
DOI: 10.1371/journal.pone.0072037
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2013-replication_meta-analysis_GWAS_identified_susceptibility-pub.pdf447.17 kBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

37
checked on Oct 20, 2019

WEB OF SCIENCETM
Citations

26
checked on Jul 9, 2019

Page view(s)

98
checked on Oct 11, 2019

Download(s)

2
checked on Oct 11, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.