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A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3\u0027-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "資源タイプ(コンテンツの種類)", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "PEDIATRIC RHEUMATOLOGY.17:34(2019)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "信州大学研究者総覧へのリンク", "attribute_value_mlt": [{"subitem_link_text": "Amano, Yuji", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.jUnFumkh.html"}, {"subitem_link_text": "Kojima, Katsuhiko", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.OCcFuakh.html"}, {"subitem_link_text": "Kobayashi, Norimoto", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.jmApHVkh.html"}, {"subitem_link_text": "Motoki, Noriko", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.ghnmbhym.html"}, {"subitem_link_text": "Nakazawa, Yozo", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.yCSFuNkh.html"}, {"subitem_link_text": "Takeshita, Toshikazu", "subitem_link_url": "https://soar-rd.shinshu-u.ac.jp/profile/ja.uVLaOmSF.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000474218200001"}]}, "item_6_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "BMC"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "31269967"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://www.ncbi.nlm.nih.gov/pubmed/31269967", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1186/s12969-019-0337-2"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1186/s12969-019-0337-2", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated."}]}, "item_6_select_64": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1546-0096", "subitem_source_identifier_type": "EISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1546-0096", "subitem_source_identifier_type": "EISSN"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "GENOME-WIDE ASSOCIATION; GAMMA-GLOBULIN TREATMENT; SUSCEPTIBILITY; INTERLEUKIN-4; PREDICTION; ATOPY; INFLAMMATION; POLYMORPHISM; RETREATMENT; RESISTANCE"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3\u0027-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients."}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Kawasaki disease; Interleukin-4 receptor; IVIG-resistance; Single nucleotide variant"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Amano, Yuji", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110251", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Akazawa, Yohei", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110252", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yasuda, Jun", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110253", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yoshino, Kazuhisa", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110254", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kojima, Katsuhiko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110255", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kobayashi, Norimoto", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110256", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Matsuzaki, Satoshi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110257", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nagasaki, Masao", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110258", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kawai, Yosuke", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110259", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Minegishi, Naoko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110260", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ishida, Noriko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110261", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Motoki, Noriko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110262", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hachiya, Akira", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110263", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nakazawa, Yozo", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110264", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yamamoto, Masayuki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110265", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Koike, Kenichi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110266", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Takeshita, Toshikazu", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "110267", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2021-02-15"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "16K10020_01.pdf", "filesize": [{"value": "928.5 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
http://hdl.handle.net/10091/00022514
http://hdl.handle.net/10091/000225149f1b0d71-e076-4cf3-8ce9-27cfb5516292
名前 / ファイル | ライセンス | アクション |
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16K10020_01.pdf (928.5 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-02-15 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題 | Kawasaki disease, Interleukin-4 receptor, IVIG-resistance, Single nucleotide variant | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Amano, Yuji
× Amano, Yuji× Akazawa, Yohei× Yasuda, Jun× Yoshino, Kazuhisa× Kojima, Katsuhiko× Kobayashi, Norimoto× Matsuzaki, Satoshi× Nagasaki, Masao× Kawai, Yosuke× Minegishi, Naoko× Ishida, Noriko× Motoki, Noriko× Hachiya, Akira× Nakazawa, Yozo× Yamamoto, Masayuki× Koike, Kenichi× Takeshita, Toshikazu |
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信州大学研究者総覧へのリンク | ||||||
氏名 | Amano, Yuji | |||||
URL | https://soar-rd.shinshu-u.ac.jp/profile/ja.jUnFumkh.html | |||||
信州大学研究者総覧へのリンク | ||||||
氏名 | Kojima, Katsuhiko | |||||
URL | https://soar-rd.shinshu-u.ac.jp/profile/ja.OCcFuakh.html | |||||
信州大学研究者総覧へのリンク | ||||||
氏名 | Kobayashi, Norimoto | |||||
URL | https://soar-rd.shinshu-u.ac.jp/profile/ja.jmApHVkh.html | |||||
信州大学研究者総覧へのリンク | ||||||
氏名 | Motoki, Noriko | |||||
URL | https://soar-rd.shinshu-u.ac.jp/profile/ja.ghnmbhym.html | |||||
信州大学研究者総覧へのリンク | ||||||
氏名 | Nakazawa, Yozo | |||||
URL | https://soar-rd.shinshu-u.ac.jp/profile/ja.yCSFuNkh.html | |||||
信州大学研究者総覧へのリンク | ||||||
氏名 | Takeshita, Toshikazu | |||||
URL | https://soar-rd.shinshu-u.ac.jp/profile/ja.uVLaOmSF.html | |||||
出版者 | ||||||
出版者 | BMC | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | PEDIATRIC RHEUMATOLOGY.17:34(2019) | |||||
書誌情報 |
PEDIATRIC RHEUMATOLOGY 巻 17, p. 34, 発行日 2019-07-03 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Article | |||||
ISSN | ||||||
収録物識別子タイプ | EISSN | |||||
収録物識別子 | 1546-0096 | |||||
PubMed | ||||||
識別子タイプ | PMID | |||||
関連識別子 | https://www.ncbi.nlm.nih.gov/pubmed/31269967 | |||||
関連名称 | 31269967 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1186/s12969-019-0337-2 | |||||
関連名称 | 10.1186/s12969-019-0337-2 | |||||
権利 | ||||||
権利情報 | © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
WoS | ||||||
表示名 | Web of Science | |||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000474218200001 |