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Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease
Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we perf...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590908/ https://www.ncbi.nlm.nih.gov/pubmed/28886140 http://dx.doi.org/10.1371/journal.pone.0184248 |
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author | Kwon, Young-Chang 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 Ebata, Ryota Hamada, Hiromichi Suzuki, Hiroyuki Ito, Kaoru Onouchi, Yoshihiro Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk |
author_facet | Kwon, Young-Chang 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 Ebata, Ryota Hamada, Hiromichi Suzuki, Hiroyuki Ito, Kaoru Onouchi, Yoshihiro Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk |
author_sort | Kwon, Young-Chang |
collection | PubMed |
description | Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we performed a sex-stratified genome-wide association study (GWAS), using the Illumina HumanOmni1-Quad BeadChip data (249 cases and 1,000 controls) and a replication study for the 34 sex-specific candidate SNPs in an independent sample set (671 cases and 3,553 controls). Male-specific associations were detected in three common variants: rs1801274 in FCGR2A [odds ratio (OR) = 1.40, P = 9.31 × 10(−5)], rs12516652 in SEMA6A (OR = 1.87, P = 3.12 × 10(−4)), and rs5771303 near IL17REL (OR = 1.57, P = 2.53 × 10(−5)). The male-specific association of FCGR2A, but not SEMA6A and IL17REL, was also replicated in a Japanese population (OR = 1.74, P = 1.04 × 10(−4) in males vs. OR = 1.22, P = 0.191 in females). In a meta-analysis with 1,461 cases and 5,302 controls, a very strong association of KD with the nonsynonymous SNP rs1801274 (p.His167Arg, previously assigned as p.His131Arg) in FCGR2A was confirmed in males (OR = 1.48, P = 1.43 × 10(−7)), but not in the females (OR = 1.17, P = 0.055). The present study demonstrates that p.His167Arg, a KD-associated FCGR2A variant, acts as a susceptibility gene in males only. Overall, the gender differences associated with FCGR2A in KD provide a new insight into KD susceptibility. |
format | Online Article Text |
id | pubmed-5590908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55909082017-09-15 Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease Kwon, Young-Chang 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 Ebata, Ryota Hamada, Hiromichi Suzuki, Hiroyuki Ito, Kaoru Onouchi, Yoshihiro Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk PLoS One Research Article Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we performed a sex-stratified genome-wide association study (GWAS), using the Illumina HumanOmni1-Quad BeadChip data (249 cases and 1,000 controls) and a replication study for the 34 sex-specific candidate SNPs in an independent sample set (671 cases and 3,553 controls). Male-specific associations were detected in three common variants: rs1801274 in FCGR2A [odds ratio (OR) = 1.40, P = 9.31 × 10(−5)], rs12516652 in SEMA6A (OR = 1.87, P = 3.12 × 10(−4)), and rs5771303 near IL17REL (OR = 1.57, P = 2.53 × 10(−5)). The male-specific association of FCGR2A, but not SEMA6A and IL17REL, was also replicated in a Japanese population (OR = 1.74, P = 1.04 × 10(−4) in males vs. OR = 1.22, P = 0.191 in females). In a meta-analysis with 1,461 cases and 5,302 controls, a very strong association of KD with the nonsynonymous SNP rs1801274 (p.His167Arg, previously assigned as p.His131Arg) in FCGR2A was confirmed in males (OR = 1.48, P = 1.43 × 10(−7)), but not in the females (OR = 1.17, P = 0.055). The present study demonstrates that p.His167Arg, a KD-associated FCGR2A variant, acts as a susceptibility gene in males only. Overall, the gender differences associated with FCGR2A in KD provide a new insight into KD susceptibility. Public Library of Science 2017-09-08 /pmc/articles/PMC5590908/ /pubmed/28886140 http://dx.doi.org/10.1371/journal.pone.0184248 Text en © 2017 Kwon et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kwon, Young-Chang 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 Ebata, Ryota Hamada, Hiromichi Suzuki, Hiroyuki Ito, Kaoru Onouchi, Yoshihiro Hong, Young Mi Jang, Gi Young Lee, Jong-Keuk Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease |
title | Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease |
title_full | Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease |
title_fullStr | Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease |
title_full_unstemmed | Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease |
title_short | Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease |
title_sort | male-specific association of the fcgr2a his167arg polymorphism with kawasaki disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590908/ https://www.ncbi.nlm.nih.gov/pubmed/28886140 http://dx.doi.org/10.1371/journal.pone.0184248 |
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