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Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A
BACKGROUND AND OBJECTIVES: Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. METHODS:...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Society of Cardiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331319/ https://www.ncbi.nlm.nih.gov/pubmed/30468029 http://dx.doi.org/10.4070/kcj.2018.0224 |
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author | Sim, Bo Kyung Park, Hyein Kim, Jae-Jung Yun, Sin Weon Yu, Jeong Jin Yoon, Kyung Lim Lee, Kyung-Yil Kil, Hong-Ryang Kim, Gi Beom Han, Myung-Ki Song, Min Seob Lee, Hyoung Doo Ha, Kee Soo Sohn, Sejung Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk |
author_facet | Sim, Bo Kyung Park, Hyein Kim, Jae-Jung Yun, Sin Weon Yu, Jeong Jin Yoon, Kyung Lim Lee, Kyung-Yil Kil, Hong-Ryang Kim, Gi Beom Han, Myung-Ki Song, Min Seob Lee, Hyoung Doo Ha, Kee Soo Sohn, Sejung Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk |
author_sort | Sim, Bo Kyung |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. METHODS: We performed a genetic association analysis in several KD subgroups categorized by clinical characteristics using the KD-associated variants of the B lymphoid tyrosine kinase (BLK; rs6993775) and Fc gamma receptor II a (FCGR2A; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples. RESULTS: BLK and FCGR2A were very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10(−11) for BLK, and OR, 1.26; p=1.42×10(−4) for FCGR2A). However, in KD subgroup analysis, we found that neither BLK nor FCGR2A were associated with either incomplete Kawasaki disease (iKD) type patients or those older than 5 years of age (p>0.2), suggesting that patients with iKD or those older than 5 years of age are a unique subgroup of KD. In genetic association analysis after excluding iKD patients and those older than 5 years old, we found that BLK was associated with all KD subgroups, whereas FCGR2A was specifically associated with male KD patients younger than 1 year of age (OR, 2.22; p=2.35×10(−5)). CONCLUSIONS: KD is a clinically and genetically heterogeneous disease. These findings will provide new insights into the clinical and genetic heterogeneity of KD. |
format | Online Article Text |
id | pubmed-6331319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Korean Society of Cardiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-63313192019-01-22 Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A Sim, Bo Kyung Park, Hyein Kim, Jae-Jung Yun, Sin Weon Yu, Jeong Jin Yoon, Kyung Lim Lee, Kyung-Yil Kil, Hong-Ryang Kim, Gi Beom Han, Myung-Ki Song, Min Seob Lee, Hyoung Doo Ha, Kee Soo Sohn, Sejung Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk Korean Circ J Original Article BACKGROUND AND OBJECTIVES: Patients with Kawasaki disease (KD) are clinically heterogeneous because its diagnosis is based solely on clinical observation and there are no definitive biomarkers. We dissected the clinical heterogeneity of KD patients using the KD-associated genetic variants. METHODS: We performed a genetic association analysis in several KD subgroups categorized by clinical characteristics using the KD-associated variants of the B lymphoid tyrosine kinase (BLK; rs6993775) and Fc gamma receptor II a (FCGR2A; rs1801274) in a large number of case (n=1,011) and control (n=4,533) samples. RESULTS: BLK and FCGR2A were very significantly associated with KD in Korean KD patients (odds ratio [OR],1.48; p=4.63×10(−11) for BLK, and OR, 1.26; p=1.42×10(−4) for FCGR2A). However, in KD subgroup analysis, we found that neither BLK nor FCGR2A were associated with either incomplete Kawasaki disease (iKD) type patients or those older than 5 years of age (p>0.2), suggesting that patients with iKD or those older than 5 years of age are a unique subgroup of KD. In genetic association analysis after excluding iKD patients and those older than 5 years old, we found that BLK was associated with all KD subgroups, whereas FCGR2A was specifically associated with male KD patients younger than 1 year of age (OR, 2.22; p=2.35×10(−5)). CONCLUSIONS: KD is a clinically and genetically heterogeneous disease. These findings will provide new insights into the clinical and genetic heterogeneity of KD. The Korean Society of Cardiology 2018-10-19 /pmc/articles/PMC6331319/ /pubmed/30468029 http://dx.doi.org/10.4070/kcj.2018.0224 Text en Copyright © 2019. The Korean Society of Cardiology https://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Sim, Bo Kyung Park, Hyein Kim, Jae-Jung Yun, Sin Weon Yu, Jeong Jin Yoon, Kyung Lim Lee, Kyung-Yil Kil, Hong-Ryang Kim, Gi Beom Han, Myung-Ki Song, Min Seob Lee, Hyoung Doo Ha, Kee Soo Sohn, Sejung Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A |
title | Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A |
title_full | Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A |
title_fullStr | Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A |
title_full_unstemmed | Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A |
title_short | Assessment of the Clinical Heterogeneity of Kawasaki Disease Using Genetic Variants of BLK and FCGR2A |
title_sort | assessment of the clinical heterogeneity of kawasaki disease using genetic variants of blk and fcgr2a |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331319/ https://www.ncbi.nlm.nih.gov/pubmed/30468029 http://dx.doi.org/10.4070/kcj.2018.0224 |
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