Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients

Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to no...
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Autor*in:	Kamal El-Din, Mennat-Allah [verfasserIn] Farhan, Marwa Salah [verfasserIn] El Shiha, Randa Ibrahim [verfasserIn] El-Kaffas, Rania Mohammed Helmy [verfasserIn] Mousa, Somaia Mohammed [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Schlagwörter:	Warfarin International Normalize Ratio Warfarin Dose CYP2C9 Genotype Target International Normalize Ratio

Übergeordnetes Werk:	Enthalten in: Pediatric drugs - Berlin [u.a.] : Springer, 1999, 16(2014), 4 vom: 06. Mai, Seite 337-341
Übergeordnetes Werk:	volume:16 ; year:2014 ; number:4 ; day:06 ; month:05 ; pages:337-341

Links:	Volltext

DOI / URN:	10.1007/s40272-014-0073-5

Katalog-ID:	SPR033313830

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520			\|a Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.
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700	1		\|a Mousa, Somaia Mohammed \|e verfasserin \|4 aut
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912			\|a GBV_ILN_95
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912			\|a GBV_ILN_110
912			\|a GBV_ILN_120
912			\|a GBV_ILN_138
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
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912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_250
912			\|a GBV_ILN_266
912			\|a GBV_ILN_281
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_370
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912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2057
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912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
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912			\|a GBV_ILN_2106
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912			\|a GBV_ILN_4037
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author_variant	e d m a k edma edmak m s f ms msf s r i e sri srie r m h e k rmhe rmhek s m m sm smm
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allfields	10.1007/s40272-014-0073-5 doi (DE-627)SPR033313830 (SPR)s40272-014-0073-5-e DE-627 ger DE-627 rakwb eng 610 ASE Kamal El-Din, Mennat-Allah verfasserin aut Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 CYP2C9 Genotype (dpeaa)DE-He213 Target International Normalize Ratio (dpeaa)DE-He213 Farhan, Marwa Salah verfasserin aut El Shiha, Randa Ibrahim verfasserin aut El-Kaffas, Rania Mohammed Helmy verfasserin aut Mousa, Somaia Mohammed verfasserin aut Enthalten in Pediatric drugs Berlin [u.a.] : Springer, 1999 16(2014), 4 vom: 06. Mai, Seite 337-341 (DE-627)327644214 (DE-600)2043681-6 1179-2019 nnns volume:16 year:2014 number:4 day:06 month:05 pages:337-341 https://dx.doi.org/10.1007/s40272-014-0073-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 16 2014 4 06 05 337-341
spelling	10.1007/s40272-014-0073-5 doi (DE-627)SPR033313830 (SPR)s40272-014-0073-5-e DE-627 ger DE-627 rakwb eng 610 ASE Kamal El-Din, Mennat-Allah verfasserin aut Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 CYP2C9 Genotype (dpeaa)DE-He213 Target International Normalize Ratio (dpeaa)DE-He213 Farhan, Marwa Salah verfasserin aut El Shiha, Randa Ibrahim verfasserin aut El-Kaffas, Rania Mohammed Helmy verfasserin aut Mousa, Somaia Mohammed verfasserin aut Enthalten in Pediatric drugs Berlin [u.a.] : Springer, 1999 16(2014), 4 vom: 06. Mai, Seite 337-341 (DE-627)327644214 (DE-600)2043681-6 1179-2019 nnns volume:16 year:2014 number:4 day:06 month:05 pages:337-341 https://dx.doi.org/10.1007/s40272-014-0073-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 16 2014 4 06 05 337-341
allfields_unstemmed	10.1007/s40272-014-0073-5 doi (DE-627)SPR033313830 (SPR)s40272-014-0073-5-e DE-627 ger DE-627 rakwb eng 610 ASE Kamal El-Din, Mennat-Allah verfasserin aut Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 CYP2C9 Genotype (dpeaa)DE-He213 Target International Normalize Ratio (dpeaa)DE-He213 Farhan, Marwa Salah verfasserin aut El Shiha, Randa Ibrahim verfasserin aut El-Kaffas, Rania Mohammed Helmy verfasserin aut Mousa, Somaia Mohammed verfasserin aut Enthalten in Pediatric drugs Berlin [u.a.] : Springer, 1999 16(2014), 4 vom: 06. Mai, Seite 337-341 (DE-627)327644214 (DE-600)2043681-6 1179-2019 nnns volume:16 year:2014 number:4 day:06 month:05 pages:337-341 https://dx.doi.org/10.1007/s40272-014-0073-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 16 2014 4 06 05 337-341
allfieldsGer	10.1007/s40272-014-0073-5 doi (DE-627)SPR033313830 (SPR)s40272-014-0073-5-e DE-627 ger DE-627 rakwb eng 610 ASE Kamal El-Din, Mennat-Allah verfasserin aut Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 CYP2C9 Genotype (dpeaa)DE-He213 Target International Normalize Ratio (dpeaa)DE-He213 Farhan, Marwa Salah verfasserin aut El Shiha, Randa Ibrahim verfasserin aut El-Kaffas, Rania Mohammed Helmy verfasserin aut Mousa, Somaia Mohammed verfasserin aut Enthalten in Pediatric drugs Berlin [u.a.] : Springer, 1999 16(2014), 4 vom: 06. Mai, Seite 337-341 (DE-627)327644214 (DE-600)2043681-6 1179-2019 nnns volume:16 year:2014 number:4 day:06 month:05 pages:337-341 https://dx.doi.org/10.1007/s40272-014-0073-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 16 2014 4 06 05 337-341
allfieldsSound	10.1007/s40272-014-0073-5 doi (DE-627)SPR033313830 (SPR)s40272-014-0073-5-e DE-627 ger DE-627 rakwb eng 610 ASE Kamal El-Din, Mennat-Allah verfasserin aut Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients. Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 CYP2C9 Genotype (dpeaa)DE-He213 Target International Normalize Ratio (dpeaa)DE-He213 Farhan, Marwa Salah verfasserin aut El Shiha, Randa Ibrahim verfasserin aut El-Kaffas, Rania Mohammed Helmy verfasserin aut Mousa, Somaia Mohammed verfasserin aut Enthalten in Pediatric drugs Berlin [u.a.] : Springer, 1999 16(2014), 4 vom: 06. Mai, Seite 337-341 (DE-627)327644214 (DE-600)2043681-6 1179-2019 nnns volume:16 year:2014 number:4 day:06 month:05 pages:337-341 https://dx.doi.org/10.1007/s40272-014-0073-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_266 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 16 2014 4 06 05 337-341
language	English
source	Enthalten in Pediatric drugs 16(2014), 4 vom: 06. Mai, Seite 337-341 volume:16 year:2014 number:4 day:06 month:05 pages:337-341
sourceStr	Enthalten in Pediatric drugs 16(2014), 4 vom: 06. Mai, Seite 337-341 volume:16 year:2014 number:4 day:06 month:05 pages:337-341
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Warfarin International Normalize Ratio Warfarin Dose CYP2C9 Genotype Target International Normalize Ratio
dewey-raw	610
isfreeaccess_bool	false
container_title	Pediatric drugs
authorswithroles_txt_mv	Kamal El-Din, Mennat-Allah @@aut@@ Farhan, Marwa Salah @@aut@@ El Shiha, Randa Ibrahim @@aut@@ El-Kaffas, Rania Mohammed Helmy @@aut@@ Mousa, Somaia Mohammed @@aut@@
publishDateDaySort_date	2014-05-06T00:00:00Z
hierarchy_top_id	327644214
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author	Kamal El-Din, Mennat-Allah
spellingShingle	Kamal El-Din, Mennat-Allah ddc 610 misc Warfarin misc International Normalize Ratio misc Warfarin Dose misc CYP2C9 Genotype misc Target International Normalize Ratio Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients
authorStr	Kamal El-Din, Mennat-Allah
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topic_title	610 ASE Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients Warfarin (dpeaa)DE-He213 International Normalize Ratio (dpeaa)DE-He213 Warfarin Dose (dpeaa)DE-He213 CYP2C9 Genotype (dpeaa)DE-He213 Target International Normalize Ratio (dpeaa)DE-He213
topic	ddc 610 misc Warfarin misc International Normalize Ratio misc Warfarin Dose misc CYP2C9 Genotype misc Target International Normalize Ratio
topic_unstemmed	ddc 610 misc Warfarin misc International Normalize Ratio misc Warfarin Dose misc CYP2C9 Genotype misc Target International Normalize Ratio
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title	Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients
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title_full	Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients
author_sort	Kamal El-Din, Mennat-Allah
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author_browse	Kamal El-Din, Mennat-Allah Farhan, Marwa Salah El Shiha, Randa Ibrahim El-Kaffas, Rania Mohammed Helmy Mousa, Somaia Mohammed
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author-letter	Kamal El-Din, Mennat-Allah
doi_str_mv	10.1007/s40272-014-0073-5
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title_sort	frequency of cyp2c9 and vkorc1 gene polymorphisms and their influence on warfarin dose in egyptian pediatric patients
title_auth	Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients
abstract	Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.
abstractGer	Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.
abstract_unstemmed	Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.
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title_short	Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients
url	https://dx.doi.org/10.1007/s40272-014-0073-5
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author2	Farhan, Marwa Salah El Shiha, Randa Ibrahim El-Kaffas, Rania Mohammed Helmy Mousa, Somaia Mohammed
author2Str	Farhan, Marwa Salah El Shiha, Randa Ibrahim El-Kaffas, Rania Mohammed Helmy Mousa, Somaia Mohammed
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doi_str	10.1007/s40272-014-0073-5
up_date	2024-07-03T17:53:50.242Z
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In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 (2 and 3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C92 (0.085), CYP2C93 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). 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Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients

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