Linked Life Data

15888487

Source:http://linkedlifedata.com/resource/pubmed/id/15888487

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2005-6-22
pubmed:abstractText
Warfarin, a commonly prescribed anticoagulant, exhibited large inter-individual and inter-ethnic differences in the dose required for its anticoagulation effect. Asian populations, including Chinese, require a much lower maintenance dose than Caucasians, for which the mechanisms still remain unknown. We determined DNA sequence variants in CYP2C9 and VKORC1 in 16 Chinese patients having warfarin sensitivity (< or = 1.5 mg/day, n = 11) or resistance (> or = 6.0 mg/day, n = 5), 104 randomly selected Chinese patients receiving warfarin, 95 normal Chinese controls and 92 normal Caucasians. We identified three CYP2C9 variants, CYP2C9*3, T299A and P382L, in four warfarin-sensitive patients. A novel VKORC1 promoter polymorphism (-1639 G > A) presented in the homozygous form (genotype AA) was found in all warfarin-sensitive patients. The resistant patients were either AG or GG. Among the 104 randomly selected Chinese patients receiving warfarin, AA genotype also had lower dose than the AG/GG genotype (P < 0.0001). Frequencies of AA, AG and GG genotypes were comparable in Chinese patients receiving warfarin (79.7, 17.6 and 2.7%) and normal Chinese controls (82, 18 and 0%), but differed significantly from Caucasians (14, 47 and 39%) (P < 0.0001). The promoter polymorphism abolished the E-box consensus sequences and dual luciferase assay revealed that VOKRC1 promoter with the G allele had a 44% increase of activity when compared with the A allele. The differences in allele frequencies of A/G allele and its levels of VKORC1 promoter activity may underscore the inter-individual differences in warfarin dosage as well as inter-ethnic differences between Chinese and Caucasians.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1745-51
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15888487-Adult, pubmed-meshheading:15888487-Aged, pubmed-meshheading:15888487-Aged, 80 and over, pubmed-meshheading:15888487-Anticoagulants, pubmed-meshheading:15888487-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:15888487-Asian Continental Ancestry Group, pubmed-meshheading:15888487-Cardiovascular Diseases, pubmed-meshheading:15888487-Drug Resistance, pubmed-meshheading:15888487-European Continental Ancestry Group, pubmed-meshheading:15888487-Female, pubmed-meshheading:15888487-Gene Frequency, pubmed-meshheading:15888487-Genotype, pubmed-meshheading:15888487-Humans, pubmed-meshheading:15888487-Male, pubmed-meshheading:15888487-Middle Aged, pubmed-meshheading:15888487-Mixed Function Oxygenases, pubmed-meshheading:15888487-Polymorphism, Single Nucleotide, pubmed-meshheading:15888487-Promoter Regions, Genetic, pubmed-meshheading:15888487-Warfarin
pubmed:year
2005
pubmed:articleTitle
A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity.
pubmed:affiliation
Institute of Biomedical Sciences, academia Sinica, Taipei, Taiwan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study