Linked Life Data

17325732

Source:http://linkedlifedata.com/resource/pubmed/id/17325732

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-1-18
pubmed:abstractText
Warfarin sodium is a vitamin K antagonist that is plagued by large variability in patient response, including higher dose requirements among African Americans. Polymorphisms in the gene encoding apolipoprotein E (APOE) may partly explain this variability by altering transport of vitamin K to the liver. In a prospective cohort study of 232 individuals (52.2% Caucasian and 47.8% African American) initiating warfarin therapy, the weekly maintenance dose was significantly higher for African Americans than for Caucasians (mean 42.9 versus mean 36.9 mg, P=0.018), and the epsilon4 allele was more common among African Americans (37.8 versus 26.4% for Caucasians). In multivariable analyses, the presence of the epsilon4 allele was associated with a statistically significantly higher warfarin dose among African Americans (median 45.0 mg in epsilon4 carriers versus 35.0 mg in non-epsilon4 carriers, P=0.014) but not Caucasians (38.1 versus 35.0 mg, P=0.60). In addition, warfarin maintenance dose increased among African Americans according to genotype previously associated with differential hepatic chylomicron clearance (epsilon2/epsilon2 or epsilon2/epsilon3: 30.0 mg; epsilon3/epsilon3: 35.0 mg; epsilon3/epsilon4 or epsilon4/epsilon4: 45.0 mg; P=0.012), although the epsilon4/epsilon4 genotype was rare and not clearly associated with higher doses. The association of APOE with warfarin dosing was independent of CYP2C9 and VKORC1 polymorphisms. APOE polymorphisms thus may be important determinants of warfarin maintenance dose and could explain at least some of the observed racial differences in dose requirements.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1470-269X
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
53-60
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17325732-African Americans, pubmed-meshheading:17325732-Aged, pubmed-meshheading:17325732-Analysis of Variance, pubmed-meshheading:17325732-Anticoagulants, pubmed-meshheading:17325732-Apolipoproteins E, pubmed-meshheading:17325732-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:17325732-Cohort Studies, pubmed-meshheading:17325732-DNA, pubmed-meshheading:17325732-European Continental Ancestry Group, pubmed-meshheading:17325732-Female, pubmed-meshheading:17325732-Genetic Variation, pubmed-meshheading:17325732-Genotype, pubmed-meshheading:17325732-Humans, pubmed-meshheading:17325732-Male, pubmed-meshheading:17325732-Middle Aged, pubmed-meshheading:17325732-Mixed Function Oxygenases, pubmed-meshheading:17325732-Prospective Studies, pubmed-meshheading:17325732-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17325732-Treatment Outcome, pubmed-meshheading:17325732-Warfarin
pubmed:year
2008
pubmed:articleTitle
Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans.
pubmed:affiliation
Department of Medicine, School of Medicine, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, USA. skimmel@cceb.med.upenn.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural