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Article: Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients

TitleGenetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients
Authors
Issue Date2001
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2001, v. 98 n. 8, p. 2584-2587 How to Cite?
AbstractCYP2C9 polymorphisms reported in Caucasians (Arg144Cys in exon 3 and Ile359Leu in exon 7) are extremely uncommon in Chinese persons. The genotype of CYP2C9 in this population was characterized to investigate its relation with the interindividual variation in warfarin dosages. Eighty-nine Chinese patients receiving warfarin were recruited. Target sequences in CYP2C9 in exons 1, 4, and 5 were amplified by polymerase chain reaction, followed by direct sequencing. Polymorphisms at 4 positions were demonstrated in exon 4. Heterozygosities for 608TTG>GTG (Leu208Val), 561CAG>CCG (GIn192Pro), 537CAT>CCT (His184Pro), and 527ATT>CTT (11e181Leu) existed at frequencies 0.75, 0.20, 0.10, and 0.09, respectively. Seventeen patients (frequency, 0.19) were homozygous for Va1208. The common genotypic combinations at these loci are Ile181/His184/ GIn192/Leu208Val (n = 50), Ile181/His184/ GIn192/Va1208 (n = 15), Ile181/His184/ GIn192/Leu208 (n = 4), Ile181/His184/ GIn192Pro/Leu208Val (n = 6), Ile181/ His184Pro/GIn192Pro/Leu208Val (n = 4), and Ile181Leu/His184/GIn 192 Pro/ Leu208Val (n = 4). At codon 208, heterozygous Leu208Val and homozygous Va1208 appeared to have a lower warfarin dose requirement than the homozygous Leu208. Patients who are heterozygous for Ile181Leu had a higher warfarin dose requirement than the homozygous llel8l. Amplified sequences in exons, I and 5 did not exhibit polymorphism. In conclusion, Chinese patients showed genetic polymorphisms of CYP2C9 in exon 4 and at codon 208; most were heterozygous Leu208Val and homozygous Va1208. Homozygous Leu208, a common allele in Caucasians, is uncommon in this cohort. The significance of these CYP2C9 polymorphic alleles remains to be determined. © 2001 by The American Society of Hematology.
Persistent Identifierhttp://hdl.handle.net/10722/78768
ISSN
2015 Impact Factor: 11.841
2015 SCImago Journal Rankings: 6.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, AYHen_HK
dc.contributor.authorChow, HCHen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorLie, AKWen_HK
dc.contributor.authorFung, ATKen_HK
dc.contributor.authorChow, WHen_HK
dc.contributor.authorYip, ASBen_HK
dc.contributor.authorLiang, Ren_HK
dc.date.accessioned2010-09-06T07:46:31Z-
dc.date.available2010-09-06T07:46:31Z-
dc.date.issued2001en_HK
dc.identifier.citationBlood, 2001, v. 98 n. 8, p. 2584-2587en_HK
dc.identifier.issn0006-4971en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78768-
dc.description.abstractCYP2C9 polymorphisms reported in Caucasians (Arg144Cys in exon 3 and Ile359Leu in exon 7) are extremely uncommon in Chinese persons. The genotype of CYP2C9 in this population was characterized to investigate its relation with the interindividual variation in warfarin dosages. Eighty-nine Chinese patients receiving warfarin were recruited. Target sequences in CYP2C9 in exons 1, 4, and 5 were amplified by polymerase chain reaction, followed by direct sequencing. Polymorphisms at 4 positions were demonstrated in exon 4. Heterozygosities for 608TTG>GTG (Leu208Val), 561CAG>CCG (GIn192Pro), 537CAT>CCT (His184Pro), and 527ATT>CTT (11e181Leu) existed at frequencies 0.75, 0.20, 0.10, and 0.09, respectively. Seventeen patients (frequency, 0.19) were homozygous for Va1208. The common genotypic combinations at these loci are Ile181/His184/ GIn192/Leu208Val (n = 50), Ile181/His184/ GIn192/Va1208 (n = 15), Ile181/His184/ GIn192/Leu208 (n = 4), Ile181/His184/ GIn192Pro/Leu208Val (n = 6), Ile181/ His184Pro/GIn192Pro/Leu208Val (n = 4), and Ile181Leu/His184/GIn 192 Pro/ Leu208Val (n = 4). At codon 208, heterozygous Leu208Val and homozygous Va1208 appeared to have a lower warfarin dose requirement than the homozygous Leu208. Patients who are heterozygous for Ile181Leu had a higher warfarin dose requirement than the homozygous llel8l. Amplified sequences in exons, I and 5 did not exhibit polymorphism. In conclusion, Chinese patients showed genetic polymorphisms of CYP2C9 in exon 4 and at codon 208; most were heterozygous Leu208Val and homozygous Va1208. Homozygous Leu208, a common allele in Caucasians, is uncommon in this cohort. The significance of these CYP2C9 polymorphic alleles remains to be determined. © 2001 by The American Society of Hematology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_HK
dc.relation.ispartofBlooden_HK
dc.subject.meshAllelesen_HK
dc.subject.meshAmino Acid Substitutionen_HK
dc.subject.meshAryl Hydrocarbon Hydroxylasesen_HK
dc.subject.meshAsian Continental Ancestry Group - geneticsen_HK
dc.subject.meshChinaen_HK
dc.subject.meshCytochrome P-450 Enzyme System - geneticsen_HK
dc.subject.meshExonsen_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshHumansen_HK
dc.subject.meshPolymorphism, Geneticen_HK
dc.subject.meshSteroid 16-alpha-Hydroxylaseen_HK
dc.subject.meshSteroid Hydroxylases - geneticsen_HK
dc.subject.meshWarfarin - adverse effectsen_HK
dc.titleGenetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patientsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-4971&volume=98&spage=2584&epage=7&date=2001&atitle=Genetic+polymorphism+in+exon+4+of+cytochrome+P450+CYP2C9+may+be+associated+with+warfarin+sensitivity+in+Chinese+patients.en_HK
dc.identifier.emailLeung, AYH:ayhleung@hku.hken_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.emailLiang, R:rliang@hku.hken_HK
dc.identifier.authorityLeung, AYH=rp00265en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1182/blood.V98.8.2584en_HK
dc.identifier.pmid11588061-
dc.identifier.scopuseid_2-s2.0-0035889154en_HK
dc.identifier.hkuros66685en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035889154&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume98en_HK
dc.identifier.issue8en_HK
dc.identifier.spage2584en_HK
dc.identifier.epage2587en_HK
dc.identifier.isiWOS:000171584000043-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, AYH=7403012668en_HK
dc.identifier.scopusauthoridChow, HCH=7102303391en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK
dc.identifier.scopusauthoridLie, AKW=24284842400en_HK
dc.identifier.scopusauthoridFung, ATK=7101926728en_HK
dc.identifier.scopusauthoridChow, WH=36852689900en_HK
dc.identifier.scopusauthoridYip, ASB=36951026000en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK

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