Linked Life Data

18328811

Source:http://linkedlifedata.com/resource/pubmed/id/18328811

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-31
pubmed:abstractText
Carboxylesterase 1 (CES1) is involved in metabolic activation of a variety of prodrugs into active derivatives and plays an important role in pharmacokinetics. We previously reported that a single nucleotide polymorphism (SNP), -816A/C of the CES1A2 gene associates with the responsiveness to an angiotensin-converting enzyme (ACE) inhibitor, imidapril, whose activity is achieved by CES1. To identify relevant functional polymorphisms, we re-sequenced the CES1A2 promoter region ( approximately 1kb) in 100 Japanese hypertensive patients. Altogether 10 SNPs and one insertion/deletion (I/D) were identified, among which seven SNPs and one I/D residing between -62 and -32 were in almost complete linkage disequilibrium (D'=1.00, r2=0.97). They consisted a minor and a major haplotype, the allele frequencies of which were 22% and 74%, respectively. The minor haplotype possessed two putative Sp1 binding sites while the major haplotype did not have any Sp1 binding site. The minor haplotype had a higher transcription and Sp1 binding activities than the major haplotype, invitro. The original -816A/C was in high linkage disequilibrium with these haplotypes (D'=0.92, r2=0.85), and well agreed with the efficacy of imidapril medication. These results suggest that the Sp1 binding site variation in the CES1A2 promoter is functional, and are good candidates for the pharmacogenetic studies of CES1-activated drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
369
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
939-42
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18328811-Amino Acid Sequence, pubmed-meshheading:18328811-Angiotensin-Converting Enzyme Inhibitors, pubmed-meshheading:18328811-Antihypertensive Agents, pubmed-meshheading:18328811-Asian Continental Ancestry Group, pubmed-meshheading:18328811-Base Sequence, pubmed-meshheading:18328811-Binding Sites, pubmed-meshheading:18328811-Carboxylesterase, pubmed-meshheading:18328811-Electrophoretic Mobility Shift Assay, pubmed-meshheading:18328811-Gene Frequency, pubmed-meshheading:18328811-Haplotypes, pubmed-meshheading:18328811-Humans, pubmed-meshheading:18328811-Imidazolidines, pubmed-meshheading:18328811-Linkage Disequilibrium, pubmed-meshheading:18328811-Molecular Sequence Data, pubmed-meshheading:18328811-Polymorphism, Single Nucleotide, pubmed-meshheading:18328811-Promoter Regions, Genetic, pubmed-meshheading:18328811-Sp1 Transcription Factor
pubmed:year
2008
pubmed:articleTitle
Functional polymorphisms in carboxylesterase1A2 (CES1A2) gene involves specific protein 1 (Sp1) binding sites.
pubmed:affiliation
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
pubmed:publicationType
Journal Article