دورية أكاديمية
First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele
العنوان: | First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele |
---|---|
المؤلفون: | O'Brien, Travis J., Kidd, Robert S., Richard, Craig A.H., Ha, Ngoc Han, Witcher, Preston, Tran, Linda V., Barbour, April, Tuck, Matthew, McIntosh, Samantha D., Douglas, Jacqueline N., Harralson, Arthur F. |
المصدر: | Medicine Faculty Publications |
بيانات النشر: | Health Sciences Research Commons |
سنة النشر: | 2013 |
المجموعة: | George Washington University: Health Sciences Research Commons (HSRC) |
مصطلحات موضوعية: | CYP2C9, Rs9332239, Warfarin |
الوقت: | 12 |
الوصف: | Background: Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. Cases: Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4. ±. 7.94. mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2. ±. 12.65. mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. Conclusions: There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements. © 2013 Elsevier B.V. |
نوع الوثيقة: | text |
اللغة: | unknown |
العلاقة: | https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3962Test; https://doi.org/10.1016/j.cca.2013.05.008Test |
DOI: | 10.1016/j.cca.2013.05.008 |
الإتاحة: | https://doi.org/10.1016/j.cca.2013.05.008Test https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3962Test |
رقم الانضمام: | edsbas.2017305D |
قاعدة البيانات: | BASE |
ResultId |
1 |
---|---|
Header |
edsbas BASE edsbas.2017305D 777 3 Academic Journal academicJournal 776.889038085938 |
PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.2017305D&custid=s6537998&authtype=sso |
FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://doi.org/10.1016/j.cca.2013.05.008# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) ) |
Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22O'Brien%2C+Travis+J%2E%22">O'Brien, Travis J.</searchLink><br /><searchLink fieldCode="AR" term="%22Kidd%2C+Robert+S%2E%22">Kidd, Robert S.</searchLink><br /><searchLink fieldCode="AR" term="%22Richard%2C+Craig+A%2EH%2E%22">Richard, Craig A.H.</searchLink><br /><searchLink fieldCode="AR" term="%22Ha%2C+Ngoc+Han%22">Ha, Ngoc Han</searchLink><br /><searchLink fieldCode="AR" term="%22Witcher%2C+Preston%22">Witcher, Preston</searchLink><br /><searchLink fieldCode="AR" term="%22Tran%2C+Linda+V%2E%22">Tran, Linda V.</searchLink><br /><searchLink fieldCode="AR" term="%22Barbour%2C+April%22">Barbour, April</searchLink><br /><searchLink fieldCode="AR" term="%22Tuck%2C+Matthew%22">Tuck, Matthew</searchLink><br /><searchLink fieldCode="AR" term="%22McIntosh%2C+Samantha+D%2E%22">McIntosh, Samantha D.</searchLink><br /><searchLink fieldCode="AR" term="%22Douglas%2C+Jacqueline+N%2E%22">Douglas, Jacqueline N.</searchLink><br /><searchLink fieldCode="AR" term="%22Harralson%2C+Arthur+F%2E%22">Harralson, Arthur F.</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Medicine Faculty Publications ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Health Sciences Research Commons ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2013 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => George Washington University: Health Sciences Research Commons (HSRC) ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22CYP2C9%22">CYP2C9</searchLink><br /><searchLink fieldCode="DE" term="%22Rs9332239%22">Rs9332239</searchLink><br /><searchLink fieldCode="DE" term="%22Warfarin%22">Warfarin</searchLink> ) Array ( [Name] => Subject [Label] => Time [Group] => Su [Data] => 12 ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Background: Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. Cases: Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4. ±. 7.94. mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2. ±. 12.65. mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. Conclusions: There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements. © 2013 Elsevier B.V. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => text ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => unknown ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3962; https://doi.org/10.1016/j.cca.2013.05.008 ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.1016/j.cca.2013.05.008 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => https://doi.org/10.1016/j.cca.2013.05.008<br />https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3962 ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.2017305D ) |
RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1016/j.cca.2013.05.008
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => unknown
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => CYP2C9
[Type] => general
)
[1] => Array
(
[SubjectFull] => Rs9332239
[Type] => general
)
[2] => Array
(
[SubjectFull] => Warfarin
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => O'Brien, Travis J.
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kidd, Robert S.
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Richard, Craig A.H.
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ha, Ngoc Han
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Witcher, Preston
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Tran, Linda V.
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Barbour, April
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Tuck, Matthew
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => McIntosh, Samantha D.
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Douglas, Jacqueline N.
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Harralson, Arthur F.
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2013
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Medicine Faculty Publications
[Type] => main
)
)
)
)
)
)
)
|
IllustrationInfo |