HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity.

The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and I...
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Autor*in:	Camilla Stephens [verfasserIn] Miguel-Ángel López-Nevot [verfasserIn] Francisco Ruiz-Cabello [verfasserIn] Eugenia Ulzurrun [verfasserIn] Germán Soriano [verfasserIn] Manuel Romero-Gómez [verfasserIn] Antonia Moreno-Casares [verfasserIn] M Isabel Lucena [verfasserIn] Raúl J Andrade [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 8(2013), 7, p e68111
Übergeordnetes Werk:	volume:8 ; year:2013 ; number:7, p e68111

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0068111

Katalog-ID:	DOAJ010335684

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520			\|a The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.
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allfields	10.1371/journal.pone.0068111 doi (DE-627)DOAJ010335684 (DE-599)DOAJ1a097bbd841f4ce782a60b3c40613893 DE-627 ger DE-627 rakwb eng Camilla Stephens verfasserin aut HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. Medicine R Science Q Miguel-Ángel López-Nevot verfasserin aut Francisco Ruiz-Cabello verfasserin aut Eugenia Ulzurrun verfasserin aut Germán Soriano verfasserin aut Manuel Romero-Gómez verfasserin aut Antonia Moreno-Casares verfasserin aut M Isabel Lucena verfasserin aut Raúl J Andrade verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e68111 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e68111 https://doi.org/10.1371/journal.pone.0068111 kostenfrei https://doaj.org/article/1a097bbd841f4ce782a60b3c40613893 kostenfrei http://europepmc.org/articles/PMC3706603?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e68111
spelling	10.1371/journal.pone.0068111 doi (DE-627)DOAJ010335684 (DE-599)DOAJ1a097bbd841f4ce782a60b3c40613893 DE-627 ger DE-627 rakwb eng Camilla Stephens verfasserin aut HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. Medicine R Science Q Miguel-Ángel López-Nevot verfasserin aut Francisco Ruiz-Cabello verfasserin aut Eugenia Ulzurrun verfasserin aut Germán Soriano verfasserin aut Manuel Romero-Gómez verfasserin aut Antonia Moreno-Casares verfasserin aut M Isabel Lucena verfasserin aut Raúl J Andrade verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e68111 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e68111 https://doi.org/10.1371/journal.pone.0068111 kostenfrei https://doaj.org/article/1a097bbd841f4ce782a60b3c40613893 kostenfrei http://europepmc.org/articles/PMC3706603?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e68111
allfields_unstemmed	10.1371/journal.pone.0068111 doi (DE-627)DOAJ010335684 (DE-599)DOAJ1a097bbd841f4ce782a60b3c40613893 DE-627 ger DE-627 rakwb eng Camilla Stephens verfasserin aut HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. Medicine R Science Q Miguel-Ángel López-Nevot verfasserin aut Francisco Ruiz-Cabello verfasserin aut Eugenia Ulzurrun verfasserin aut Germán Soriano verfasserin aut Manuel Romero-Gómez verfasserin aut Antonia Moreno-Casares verfasserin aut M Isabel Lucena verfasserin aut Raúl J Andrade verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e68111 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e68111 https://doi.org/10.1371/journal.pone.0068111 kostenfrei https://doaj.org/article/1a097bbd841f4ce782a60b3c40613893 kostenfrei http://europepmc.org/articles/PMC3706603?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e68111
allfieldsGer	10.1371/journal.pone.0068111 doi (DE-627)DOAJ010335684 (DE-599)DOAJ1a097bbd841f4ce782a60b3c40613893 DE-627 ger DE-627 rakwb eng Camilla Stephens verfasserin aut HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. Medicine R Science Q Miguel-Ángel López-Nevot verfasserin aut Francisco Ruiz-Cabello verfasserin aut Eugenia Ulzurrun verfasserin aut Germán Soriano verfasserin aut Manuel Romero-Gómez verfasserin aut Antonia Moreno-Casares verfasserin aut M Isabel Lucena verfasserin aut Raúl J Andrade verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e68111 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e68111 https://doi.org/10.1371/journal.pone.0068111 kostenfrei https://doaj.org/article/1a097bbd841f4ce782a60b3c40613893 kostenfrei http://europepmc.org/articles/PMC3706603?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e68111
allfieldsSound	10.1371/journal.pone.0068111 doi (DE-627)DOAJ010335684 (DE-599)DOAJ1a097bbd841f4ce782a60b3c40613893 DE-627 ger DE-627 rakwb eng Camilla Stephens verfasserin aut HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. Medicine R Science Q Miguel-Ángel López-Nevot verfasserin aut Francisco Ruiz-Cabello verfasserin aut Eugenia Ulzurrun verfasserin aut Germán Soriano verfasserin aut Manuel Romero-Gómez verfasserin aut Antonia Moreno-Casares verfasserin aut M Isabel Lucena verfasserin aut Raúl J Andrade verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 8(2013), 7, p e68111 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:8 year:2013 number:7, p e68111 https://doi.org/10.1371/journal.pone.0068111 kostenfrei https://doaj.org/article/1a097bbd841f4ce782a60b3c40613893 kostenfrei http://europepmc.org/articles/PMC3706603?pdf=render kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2013 7, p e68111
language	English
source	In PLoS ONE 8(2013), 7, p e68111 volume:8 year:2013 number:7, p e68111
sourceStr	In PLoS ONE 8(2013), 7, p e68111 volume:8 year:2013 number:7, p e68111
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institution	findex.gbv.de
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container_title	PLoS ONE
authorswithroles_txt_mv	Camilla Stephens @@aut@@ Miguel-Ángel López-Nevot @@aut@@ Francisco Ruiz-Cabello @@aut@@ Eugenia Ulzurrun @@aut@@ Germán Soriano @@aut@@ Manuel Romero-Gómez @@aut@@ Antonia Moreno-Casares @@aut@@ M Isabel Lucena @@aut@@ Raúl J Andrade @@aut@@
publishDateDaySort_date	2013-01-01T00:00:00Z
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author	Camilla Stephens
spellingShingle	Camilla Stephens misc Medicine misc R misc Science misc Q HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity.
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topic_title	HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity
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title	HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity.
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title_full	HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity
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author_browse	Camilla Stephens Miguel-Ángel López-Nevot Francisco Ruiz-Cabello Eugenia Ulzurrun Germán Soriano Manuel Romero-Gómez Antonia Moreno-Casares M Isabel Lucena Raúl J Andrade
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title_sort	hla alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity
title_auth	HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity.
abstract	The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.
abstractGer	The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.
abstract_unstemmed	The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.
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title_short	HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity.
url	https://doi.org/10.1371/journal.pone.0068111 https://doaj.org/article/1a097bbd841f4ce782a60b3c40613893 http://europepmc.org/articles/PMC3706603?pdf=render https://doaj.org/toc/1932-6203
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Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases.High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.The distributions of class I alleles A3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB11501-DQB10602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A3002 and/or B1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB11501-DQB10602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB10301-DQB10201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB11302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07).HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Science</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Q</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Miguel-Ángel López-Nevot</subfield><subfield code="e">verfasserin</subfield><subfield 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HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity.

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