Characterization of a Novel CYP2C9 Mutation (1009C>A) Detected in a Warfarin-Sensitive Patient

Bibliographic Details
Title:	Characterization of a Novel CYP2C9 Mutation (1009C>A) Detected in a Warfarin-Sensitive Patient
Authors:	Shun-Bin Luo, Chuan-Bao Li, Da-Peng Dai, Shuang-Hu Wang, Zhen-He Wang, Pei-Wu Geng, Jie Cai, Zhe-Li Jiang, Cheng-Wei Pu, Ke Shang, Xin-Min Yuan, Ya-Po Cao, Guo-Xin Hu, Jian-Ping Cai
Source:	Journal of Pharmacological Sciences, Vol 125, Iss 2, Pp 150-156 (2014)
Publisher Information:	Elsevier, 2014.
Publication Year:	2014
Collection:	LCC:Therapeutics. Pharmacology
Subject Terms:	Therapeutics. Pharmacology, RM1-950
More Details:	Abstract.: Warfarin is the most frequently prescribed anticoagulant for the long-term treatment in the clinic. Recent studies have shown that polymorphic alleles within the CYP2C9, VKORC1, and CYP4F2 genes are related to the warfarin dosage requirement. In this study, a novel nonsynonymous mutation (1009C>A) in CYP2C9 was detected in a warfarin-hypersensitive patient, while the other two candidate genes were both found to be homozygous for the wild-type alleles. The newly identified point mutation results in an amino acid substitution at position 337 of the CYP2C9 protein (P337T) and has been designated as the novel allele CYP2C9*58. When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. These data suggested that when compared with wild-type CYP2C9.1, the enzymatic activity of the novel allelic variant has been greatly reduced by the 1009C>A mutation. If patients carrying this allele take drugs metabolized by CYP2C9, their metabolic rate might be slower than that of wild-type allele carriers and thus much more attention should be paid to their clinical care. [Supplementary methods and Figure: available only at http://dx.doi.org/10.1254/jphs.13189FP] Keywords:: CYP2C9, allelic variant, insect cell microsome, functional analysis in vitro
Document Type:	article
File Description:	electronic resource
Language:	English
ISSN:	1347-8613
Relation:	http://www.sciencedirect.com/science/article/pii/S1347861319301379; https://doaj.org/toc/1347-8613
DOI:	10.1254/jphs.13189FP
Access URL:	https://doaj.org/article/ca8b0de2b96044acb05474074d26c394
Accession Number:	edsdoj.8b0de2b96044acb05474074d26c394
Database:	Directory of Open Access Journals

FullText	Text: Availability: 0 CustomLinks: – Url: https://www.doi.org/10.1254/jphs.13189FP? Name: ScienceDirect (all content)-s8985755 Category: fullText Text: View record from ScienceDirect MouseOverText: View record from ScienceDirect – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edsdoj&genre=article&issn=13478613&ISBN=&volume=125&issue=2&date=20140101&spage=150&pages=150-156&title=Journal of Pharmacological Sciences&atitle=Characterization%20of%20a%20Novel%20CYP2C9%20Mutation%20%281009C%3EA%29%20Detected%20in%20a%20Warfarin-Sensitive%20Patient&aulast=Shun-Bin%20Luo&id=DOI:10.1254/jphs.13189FP Name: Full Text Finder (for New FTF UI) (s8985755) Category: fullText Text: Find It @ SCU Libraries MouseOverText: Find It @ SCU Libraries – Url: https://doaj.org/article/ca8b0de2b96044acb05474074d26c394 Name: EDS - DOAJ (s8985755) Category: fullText Text: View record from DOAJ MouseOverText: View record from DOAJ
Header	DbId: edsdoj DbLabel: Directory of Open Access Journals An: edsdoj.8b0de2b96044acb05474074d26c394 RelevancyScore: 873 AccessLevel: 3 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 873.219055175781
IllustrationInfo
Items	– Name: Title Label: Title Group: Ti Data: Characterization of a Novel CYP2C9 Mutation (1009C>A) Detected in a Warfarin-Sensitive Patient – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Shun-Bin+Luo%22">Shun-Bin Luo</searchLink><br /><searchLink fieldCode="AR" term="%22Chuan-Bao+Li%22">Chuan-Bao Li</searchLink><br /><searchLink fieldCode="AR" term="%22Da-Peng+Dai%22">Da-Peng Dai</searchLink><br /><searchLink fieldCode="AR" term="%22Shuang-Hu+Wang%22">Shuang-Hu Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Zhen-He+Wang%22">Zhen-He Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Pei-Wu+Geng%22">Pei-Wu Geng</searchLink><br /><searchLink fieldCode="AR" term="%22Jie+Cai%22">Jie Cai</searchLink><br /><searchLink fieldCode="AR" term="%22Zhe-Li+Jiang%22">Zhe-Li Jiang</searchLink><br /><searchLink fieldCode="AR" term="%22Cheng-Wei+Pu%22">Cheng-Wei Pu</searchLink><br /><searchLink fieldCode="AR" term="%22Ke+Shang%22">Ke Shang</searchLink><br /><searchLink fieldCode="AR" term="%22Xin-Min+Yuan%22">Xin-Min Yuan</searchLink><br /><searchLink fieldCode="AR" term="%22Ya-Po+Cao%22">Ya-Po Cao</searchLink><br /><searchLink fieldCode="AR" term="%22Guo-Xin+Hu%22">Guo-Xin Hu</searchLink><br /><searchLink fieldCode="AR" term="%22Jian-Ping+Cai%22">Jian-Ping Cai</searchLink> – Name: TitleSource Label: Source Group: Src Data: Journal of Pharmacological Sciences, Vol 125, Iss 2, Pp 150-156 (2014) – Name: Publisher Label: Publisher Information Group: PubInfo Data: Elsevier, 2014. – Name: DatePubCY Label: Publication Year Group: Date Data: 2014 – Name: Subset Label: Collection Group: HoldingsInfo Data: LCC:Therapeutics. Pharmacology – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Therapeutics%2E+Pharmacology%22">Therapeutics. Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22RM1-950%22">RM1-950</searchLink> – Name: Abstract Label: Description Group: Ab Data: Abstract.: Warfarin is the most frequently prescribed anticoagulant for the long-term treatment in the clinic. Recent studies have shown that polymorphic alleles within the CYP2C9, VKORC1, and CYP4F2 genes are related to the warfarin dosage requirement. In this study, a novel nonsynonymous mutation (1009C>A) in CYP2C9 was detected in a warfarin-hypersensitive patient, while the other two candidate genes were both found to be homozygous for the wild-type alleles. The newly identified point mutation results in an amino acid substitution at position 337 of the CYP2C9 protein (P337T) and has been designated as the novel allele CYP2C9*58. When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. These data suggested that when compared with wild-type CYP2C9.1, the enzymatic activity of the novel allelic variant has been greatly reduced by the 1009C>A mutation. If patients carrying this allele take drugs metabolized by CYP2C9, their metabolic rate might be slower than that of wild-type allele carriers and thus much more attention should be paid to their clinical care. [Supplementary methods and Figure: available only at http://dx.doi.org/10.1254/jphs.13189FP] Keywords:: CYP2C9, allelic variant, insect cell microsome, functional analysis in vitro – Name: TypeDocument Label: Document Type Group: TypDoc Data: article – Name: Format Label: File Description Group: SrcInfo Data: electronic resource – Name: Language Label: Language Group: Lang Data: English – Name: ISSN Label: ISSN Group: ISSN Data: 1347-8613 – Name: NoteTitleSource Label: Relation Group: SrcInfo Data: http://www.sciencedirect.com/science/article/pii/S1347861319301379; https://doaj.org/toc/1347-8613 – Name: DOI Label: DOI Group: ID Data: 10.1254/jphs.13189FP – Name: URL Label: Access URL Group: URL Data: <link linkTarget="URL" linkTerm="https://doaj.org/article/ca8b0de2b96044acb05474074d26c394" linkWindow="_blank">https://doaj.org/article/ca8b0de2b96044acb05474074d26c394</link> – Name: AN Label: Accession Number Group: ID Data: edsdoj.8b0de2b96044acb05474074d26c394
PLink	https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.8b0de2b96044acb05474074d26c394
RecordInfo	BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1254/jphs.13189FP Languages: – Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 150 Subjects: – SubjectFull: Therapeutics. Pharmacology Type: general – SubjectFull: RM1-950 Type: general Titles: – TitleFull: Characterization of a Novel CYP2C9 Mutation (1009C>A) Detected in a Warfarin-Sensitive Patient Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Shun-Bin Luo – PersonEntity: Name: NameFull: Chuan-Bao Li – PersonEntity: Name: NameFull: Da-Peng Dai – PersonEntity: Name: NameFull: Shuang-Hu Wang – PersonEntity: Name: NameFull: Zhen-He Wang – PersonEntity: Name: NameFull: Pei-Wu Geng – PersonEntity: Name: NameFull: Jie Cai – PersonEntity: Name: NameFull: Zhe-Li Jiang – PersonEntity: Name: NameFull: Cheng-Wei Pu – PersonEntity: Name: NameFull: Ke Shang – PersonEntity: Name: NameFull: Xin-Min Yuan – PersonEntity: Name: NameFull: Ya-Po Cao – PersonEntity: Name: NameFull: Guo-Xin Hu – PersonEntity: Name: NameFull: Jian-Ping Cai IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Type: published Y: 2014 Identifiers: – Type: issn-print Value: 13478613 Numbering: – Type: volume Value: 125 – Type: issue Value: 2 Titles: – TitleFull: Journal of Pharmacological Sciences Type: main
ResultId	1