A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease

Abstract 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. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Yuji Amano [verfasserIn] Yohei Akazawa [verfasserIn] Jun Yasuda [verfasserIn] Kazuhisa Yoshino [verfasserIn] Katsuhiko Kojima [verfasserIn] Norimoto Kobayashi [verfasserIn] Satoshi Matsuzaki [verfasserIn] Masao Nagasaki [verfasserIn] Yosuke Kawai [verfasserIn] Naoko Minegishi [verfasserIn] Noriko Ishida [verfasserIn] Noriko Motoki [verfasserIn] Akira Hachiya [verfasserIn] Yozo Nakazawa [verfasserIn] Masayuki Yamamoto [verfasserIn] Kenichi Koike [verfasserIn] Toshikazu Takeshita [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant

Übergeordnetes Werk:	In: Pediatric Rheumatology Online Journal - BMC, 2007, 17(2019), 1, Seite 11
Übergeordnetes Werk:	volume:17 ; year:2019 ; number:1 ; pages:11

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12969-019-0337-2

Katalog-ID:	DOAJ074708740

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245	1	2	\|a A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
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520			\|a Abstract 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.
650		4	\|a Kawasaki disease
650		4	\|a Interleukin-4 receptor
650		4	\|a IVIG-resistance
650		4	\|a Single nucleotide variant
653		0	\|a Pediatrics
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700	0		\|a Yohei Akazawa \|e verfasserin \|4 aut
700	0		\|a Jun Yasuda \|e verfasserin \|4 aut
700	0		\|a Kazuhisa Yoshino \|e verfasserin \|4 aut
700	0		\|a Katsuhiko Kojima \|e verfasserin \|4 aut
700	0		\|a Norimoto Kobayashi \|e verfasserin \|4 aut
700	0		\|a Satoshi Matsuzaki \|e verfasserin \|4 aut
700	0		\|a Masao Nagasaki \|e verfasserin \|4 aut
700	0		\|a Yosuke Kawai \|e verfasserin \|4 aut
700	0		\|a Naoko Minegishi \|e verfasserin \|4 aut
700	0		\|a Noriko Ishida \|e verfasserin \|4 aut
700	0		\|a Noriko Motoki \|e verfasserin \|4 aut
700	0		\|a Akira Hachiya \|e verfasserin \|4 aut
700	0		\|a Yozo Nakazawa \|e verfasserin \|4 aut
700	0		\|a Masayuki Yamamoto \|e verfasserin \|4 aut
700	0		\|a Kenichi Koike \|e verfasserin \|4 aut
700	0		\|a Toshikazu Takeshita \|e verfasserin \|4 aut
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allfields	10.1186/s12969-019-0337-2 doi (DE-627)DOAJ074708740 (DE-599)DOAJc81b1f5eef1c496ea95f66d4d530fd2b DE-627 ger DE-627 rakwb eng RJ1-570 RC925-935 Yuji Amano verfasserin aut A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant Pediatrics Diseases of the musculoskeletal system Yohei Akazawa verfasserin aut Jun Yasuda verfasserin aut Kazuhisa Yoshino verfasserin aut Katsuhiko Kojima verfasserin aut Norimoto Kobayashi verfasserin aut Satoshi Matsuzaki verfasserin aut Masao Nagasaki verfasserin aut Yosuke Kawai verfasserin aut Naoko Minegishi verfasserin aut Noriko Ishida verfasserin aut Noriko Motoki verfasserin aut Akira Hachiya verfasserin aut Yozo Nakazawa verfasserin aut Masayuki Yamamoto verfasserin aut Kenichi Koike verfasserin aut Toshikazu Takeshita verfasserin aut In Pediatric Rheumatology Online Journal BMC, 2007 17(2019), 1, Seite 11 (DE-627)527833746 (DE-600)2279468-2 15460096 nnns volume:17 year:2019 number:1 pages:11 https://doi.org/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/article/c81b1f5eef1c496ea95f66d4d530fd2b kostenfrei http://link.springer.com/article/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/toc/1546-0096 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11
spelling	10.1186/s12969-019-0337-2 doi (DE-627)DOAJ074708740 (DE-599)DOAJc81b1f5eef1c496ea95f66d4d530fd2b DE-627 ger DE-627 rakwb eng RJ1-570 RC925-935 Yuji Amano verfasserin aut A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant Pediatrics Diseases of the musculoskeletal system Yohei Akazawa verfasserin aut Jun Yasuda verfasserin aut Kazuhisa Yoshino verfasserin aut Katsuhiko Kojima verfasserin aut Norimoto Kobayashi verfasserin aut Satoshi Matsuzaki verfasserin aut Masao Nagasaki verfasserin aut Yosuke Kawai verfasserin aut Naoko Minegishi verfasserin aut Noriko Ishida verfasserin aut Noriko Motoki verfasserin aut Akira Hachiya verfasserin aut Yozo Nakazawa verfasserin aut Masayuki Yamamoto verfasserin aut Kenichi Koike verfasserin aut Toshikazu Takeshita verfasserin aut In Pediatric Rheumatology Online Journal BMC, 2007 17(2019), 1, Seite 11 (DE-627)527833746 (DE-600)2279468-2 15460096 nnns volume:17 year:2019 number:1 pages:11 https://doi.org/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/article/c81b1f5eef1c496ea95f66d4d530fd2b kostenfrei http://link.springer.com/article/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/toc/1546-0096 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11
allfields_unstemmed	10.1186/s12969-019-0337-2 doi (DE-627)DOAJ074708740 (DE-599)DOAJc81b1f5eef1c496ea95f66d4d530fd2b DE-627 ger DE-627 rakwb eng RJ1-570 RC925-935 Yuji Amano verfasserin aut A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant Pediatrics Diseases of the musculoskeletal system Yohei Akazawa verfasserin aut Jun Yasuda verfasserin aut Kazuhisa Yoshino verfasserin aut Katsuhiko Kojima verfasserin aut Norimoto Kobayashi verfasserin aut Satoshi Matsuzaki verfasserin aut Masao Nagasaki verfasserin aut Yosuke Kawai verfasserin aut Naoko Minegishi verfasserin aut Noriko Ishida verfasserin aut Noriko Motoki verfasserin aut Akira Hachiya verfasserin aut Yozo Nakazawa verfasserin aut Masayuki Yamamoto verfasserin aut Kenichi Koike verfasserin aut Toshikazu Takeshita verfasserin aut In Pediatric Rheumatology Online Journal BMC, 2007 17(2019), 1, Seite 11 (DE-627)527833746 (DE-600)2279468-2 15460096 nnns volume:17 year:2019 number:1 pages:11 https://doi.org/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/article/c81b1f5eef1c496ea95f66d4d530fd2b kostenfrei http://link.springer.com/article/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/toc/1546-0096 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11
allfieldsGer	10.1186/s12969-019-0337-2 doi (DE-627)DOAJ074708740 (DE-599)DOAJc81b1f5eef1c496ea95f66d4d530fd2b DE-627 ger DE-627 rakwb eng RJ1-570 RC925-935 Yuji Amano verfasserin aut A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant Pediatrics Diseases of the musculoskeletal system Yohei Akazawa verfasserin aut Jun Yasuda verfasserin aut Kazuhisa Yoshino verfasserin aut Katsuhiko Kojima verfasserin aut Norimoto Kobayashi verfasserin aut Satoshi Matsuzaki verfasserin aut Masao Nagasaki verfasserin aut Yosuke Kawai verfasserin aut Naoko Minegishi verfasserin aut Noriko Ishida verfasserin aut Noriko Motoki verfasserin aut Akira Hachiya verfasserin aut Yozo Nakazawa verfasserin aut Masayuki Yamamoto verfasserin aut Kenichi Koike verfasserin aut Toshikazu Takeshita verfasserin aut In Pediatric Rheumatology Online Journal BMC, 2007 17(2019), 1, Seite 11 (DE-627)527833746 (DE-600)2279468-2 15460096 nnns volume:17 year:2019 number:1 pages:11 https://doi.org/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/article/c81b1f5eef1c496ea95f66d4d530fd2b kostenfrei http://link.springer.com/article/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/toc/1546-0096 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11
allfieldsSound	10.1186/s12969-019-0337-2 doi (DE-627)DOAJ074708740 (DE-599)DOAJc81b1f5eef1c496ea95f66d4d530fd2b DE-627 ger DE-627 rakwb eng RJ1-570 RC925-935 Yuji Amano verfasserin aut A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant Pediatrics Diseases of the musculoskeletal system Yohei Akazawa verfasserin aut Jun Yasuda verfasserin aut Kazuhisa Yoshino verfasserin aut Katsuhiko Kojima verfasserin aut Norimoto Kobayashi verfasserin aut Satoshi Matsuzaki verfasserin aut Masao Nagasaki verfasserin aut Yosuke Kawai verfasserin aut Naoko Minegishi verfasserin aut Noriko Ishida verfasserin aut Noriko Motoki verfasserin aut Akira Hachiya verfasserin aut Yozo Nakazawa verfasserin aut Masayuki Yamamoto verfasserin aut Kenichi Koike verfasserin aut Toshikazu Takeshita verfasserin aut In Pediatric Rheumatology Online Journal BMC, 2007 17(2019), 1, Seite 11 (DE-627)527833746 (DE-600)2279468-2 15460096 nnns volume:17 year:2019 number:1 pages:11 https://doi.org/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/article/c81b1f5eef1c496ea95f66d4d530fd2b kostenfrei http://link.springer.com/article/10.1186/s12969-019-0337-2 kostenfrei https://doaj.org/toc/1546-0096 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2019 1 11
language	English
source	In Pediatric Rheumatology Online Journal 17(2019), 1, Seite 11 volume:17 year:2019 number:1 pages:11
sourceStr	In Pediatric Rheumatology Online Journal 17(2019), 1, Seite 11 volume:17 year:2019 number:1 pages:11
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant Pediatrics Diseases of the musculoskeletal system
isfreeaccess_bool	true
container_title	Pediatric Rheumatology Online Journal
authorswithroles_txt_mv	Yuji Amano @@aut@@ Yohei Akazawa @@aut@@ Jun Yasuda @@aut@@ Kazuhisa Yoshino @@aut@@ Katsuhiko Kojima @@aut@@ Norimoto Kobayashi @@aut@@ Satoshi Matsuzaki @@aut@@ Masao Nagasaki @@aut@@ Yosuke Kawai @@aut@@ Naoko Minegishi @@aut@@ Noriko Ishida @@aut@@ Noriko Motoki @@aut@@ Akira Hachiya @@aut@@ Yozo Nakazawa @@aut@@ Masayuki Yamamoto @@aut@@ Kenichi Koike @@aut@@ Toshikazu Takeshita @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	527833746
id	DOAJ074708740
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ074708740</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230502124421.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2019 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12969-019-0337-2</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ074708740</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJc81b1f5eef1c496ea95f66d4d530fd2b</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RJ1-570</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC925-935</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Yuji Amano</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="2"><subfield code="a">A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract 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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kawasaki disease</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Interleukin-4 receptor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IVIG-resistance</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Single nucleotide variant</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Pediatrics</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Diseases of the musculoskeletal system</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yohei Akazawa</subfield><subfield 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callnumber-first	R - Medicine
author	Yuji Amano
spellingShingle	Yuji Amano misc RJ1-570 misc RC925-935 misc Kawasaki disease misc Interleukin-4 receptor misc IVIG-resistance misc Single nucleotide variant misc Pediatrics misc Diseases of the musculoskeletal system A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
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topic_title	RJ1-570 RC925-935 A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease Kawasaki disease Interleukin-4 receptor IVIG-resistance Single nucleotide variant
topic	misc RJ1-570 misc RC925-935 misc Kawasaki disease misc Interleukin-4 receptor misc IVIG-resistance misc Single nucleotide variant misc Pediatrics misc Diseases of the musculoskeletal system
topic_unstemmed	misc RJ1-570 misc RC925-935 misc Kawasaki disease misc Interleukin-4 receptor misc IVIG-resistance misc Single nucleotide variant misc Pediatrics misc Diseases of the musculoskeletal system
topic_browse	misc RJ1-570 misc RC925-935 misc Kawasaki disease misc Interleukin-4 receptor misc IVIG-resistance misc Single nucleotide variant misc Pediatrics misc Diseases of the musculoskeletal system
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title	A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
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title_full	A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
author_sort	Yuji Amano
journal	Pediatric Rheumatology Online Journal
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author_browse	Yuji Amano Yohei Akazawa Jun Yasuda Kazuhisa Yoshino Katsuhiko Kojima Norimoto Kobayashi Satoshi Matsuzaki Masao Nagasaki Yosuke Kawai Naoko Minegishi Noriko Ishida Noriko Motoki Akira Hachiya Yozo Nakazawa Masayuki Yamamoto Kenichi Koike Toshikazu Takeshita
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title_sort	low-frequency il4r locus variant in japanese patients with intravenous immunoglobulin therapy-unresponsive kawasaki disease
callnumber	RJ1-570
title_auth	A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
abstract	Abstract 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.
abstractGer	Abstract 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.
abstract_unstemmed	Abstract 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.
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title_short	A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
url	https://doi.org/10.1186/s12969-019-0337-2 https://doaj.org/article/c81b1f5eef1c496ea95f66d4d530fd2b http://link.springer.com/article/10.1186/s12969-019-0337-2 https://doaj.org/toc/1546-0096
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author2	Yohei Akazawa Jun Yasuda Kazuhisa Yoshino Katsuhiko Kojima Norimoto Kobayashi Satoshi Matsuzaki Masao Nagasaki Yosuke Kawai Naoko Minegishi Noriko Ishida Noriko Motoki Akira Hachiya Yozo Nakazawa Masayuki Yamamoto Kenichi Koike Toshikazu Takeshita
author2Str	Yohei Akazawa Jun Yasuda Kazuhisa Yoshino Katsuhiko Kojima Norimoto Kobayashi Satoshi Matsuzaki Masao Nagasaki Yosuke Kawai Naoko Minegishi Noriko Ishida Noriko Motoki Akira Hachiya Yozo Nakazawa Masayuki Yamamoto Kenichi Koike Toshikazu Takeshita
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up_date	2024-07-04T00:16:17.527Z
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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′-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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kawasaki disease</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Interleukin-4 receptor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">IVIG-resistance</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Single nucleotide variant</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Pediatrics</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Diseases of the musculoskeletal system</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yohei Akazawa</subfield><subfield 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A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease

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