Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.

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 po...

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Autores principales:	Chia-Jung Chang, Ho-Chang Kuo, Jeng-Sheng Chang, Jong-Keuk Lee, Fuu-Jen Tsai, Chiea Chuen Khor, Li-Ching Chang, Shih-Ping Chen, Tai-Ming Ko, Yi-Min Liu, Ying-Ju Chen, Young Mi Hong, Gi Young Jang, Martin L Hibberd, Taco Kuijpers, David Burgner, Michael Levin, Jane C Burns, Sonia Davila, International Kawasaki Disease Genetics Consortium, Korean Kawasaki Disease Genetics Consortium, Taiwan Kawasaki Disease Genetics Consortium, Yuan-Tsong Chen, Chien-Hsiun Chen, Jer-Yuarn Wu, Yi-Ching Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f785e0ce8cb442d28b33506526470cec
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spelling	oai:doaj.org-article:f785e0ce8cb442d28b33506526470cec2021-11-18T08:57:39ZReplication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.1932-620310.1371/journal.pone.0072037https://doaj.org/article/f785e0ce8cb442d28b33506526470cec2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24023612/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Chia-Jung ChangHo-Chang KuoJeng-Sheng ChangJong-Keuk LeeFuu-Jen TsaiChiea Chuen KhorLi-Ching ChangShih-Ping ChenTai-Ming KoYi-Min LiuYing-Ju ChenYoung Mi HongGi Young JangMartin L HibberdTaco KuijpersDavid BurgnerMichael LevinJane C BurnsSonia DavilaInternational Kawasaki Disease Genetics ConsortiumKorean Kawasaki Disease Genetics ConsortiumTaiwan Kawasaki Disease Genetics ConsortiumYuan-Tsong ChenChien-Hsiun ChenJer-Yuarn WuYi-Ching LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72037 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chia-Jung Chang Ho-Chang Kuo Jeng-Sheng Chang Jong-Keuk Lee Fuu-Jen Tsai Chiea Chuen Khor Li-Ching Chang Shih-Ping Chen Tai-Ming Ko Yi-Min Liu Ying-Ju Chen Young Mi Hong Gi Young Jang Martin L Hibberd Taco Kuijpers David Burgner Michael Levin Jane C Burns Sonia Davila International Kawasaki Disease Genetics Consortium Korean Kawasaki Disease Genetics Consortium Taiwan Kawasaki Disease Genetics Consortium Yuan-Tsong Chen Chien-Hsiun Chen Jer-Yuarn Wu Yi-Ching Lee Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.
description	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.
format	article
author	Chia-Jung Chang Ho-Chang Kuo Jeng-Sheng Chang Jong-Keuk Lee Fuu-Jen Tsai Chiea Chuen Khor Li-Ching Chang Shih-Ping Chen Tai-Ming Ko Yi-Min Liu Ying-Ju Chen Young Mi Hong Gi Young Jang Martin L Hibberd Taco Kuijpers David Burgner Michael Levin Jane C Burns Sonia Davila International Kawasaki Disease Genetics Consortium Korean Kawasaki Disease Genetics Consortium Taiwan Kawasaki Disease Genetics Consortium Yuan-Tsong Chen Chien-Hsiun Chen Jer-Yuarn Wu Yi-Ching Lee
author_facet	Chia-Jung Chang Ho-Chang Kuo Jeng-Sheng Chang Jong-Keuk Lee Fuu-Jen Tsai Chiea Chuen Khor Li-Ching Chang Shih-Ping Chen Tai-Ming Ko Yi-Min Liu Ying-Ju Chen Young Mi Hong Gi Young Jang Martin L Hibberd Taco Kuijpers David Burgner Michael Levin Jane C Burns Sonia Davila International Kawasaki Disease Genetics Consortium Korean Kawasaki Disease Genetics Consortium Taiwan Kawasaki Disease Genetics Consortium Yuan-Tsong Chen Chien-Hsiun Chen Jer-Yuarn Wu Yi-Ching Lee
author_sort	Chia-Jung Chang
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.
title_short	Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.
title_full	Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.
title_fullStr	Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.
title_full_unstemmed	Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.
title_sort	replication and meta-analysis of gwas identified susceptibility loci in kawasaki disease confirm the importance of b lymphoid tyrosine kinase (blk) in disease susceptibility.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f785e0ce8cb442d28b33506526470cec
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Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility.

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