PMID- 18328811
OWN - NLM
STAT- MEDLINE
DCOM- 20080422
LR  - 20221207
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 369
IP  - 3
DP  - 2008 May 9
TI  - Functional polymorphisms in carboxylesterase1A2 (CES1A2) gene involves specific 
      protein 1 (Sp1) binding sites.
PG  - 939-42
LID - 10.1016/j.bbrc.2008.02.120 [doi]
AB  - 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.
FAU - Yoshimura, Mika
AU  - Yoshimura M
AD  - Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical 
      Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
FAU - Kimura, Tomomi
AU  - Kimura T
FAU - Ishii, Miho
AU  - Ishii M
FAU - Ishii, Keisuke
AU  - Ishii K
FAU - Matsuura, Tadashi
AU  - Matsuura T
FAU - Geshi, Eiichi
AU  - Geshi E
FAU - Hosokawa, Masakiyo
AU  - Hosokawa M
FAU - Muramatsu, Masaaki
AU  - Muramatsu M
LA  - eng
PT  - Journal Article
DEP - 20080306
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Imidazolidines)
RN  - 0 (Sp1 Transcription Factor)
RN  - BW7H1TJS22 (imidapril)
RN  - EC 3.1.1.1 (Carboxylesterase)
RN  - EC 3.1.1.1 (carboxylesterase 1A2, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacokinetics
MH  - Antihypertensive Agents/*pharmacokinetics
MH  - Asian People/genetics
MH  - Base Sequence
MH  - Binding Sites
MH  - Carboxylesterase/*genetics/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Frequency
MH  - Haplotypes
MH  - Humans
MH  - Imidazolidines/*pharmacokinetics
MH  - Linkage Disequilibrium
MH  - Molecular Sequence Data
MH  - *Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic
MH  - Sp1 Transcription Factor/*metabolism
EDAT- 2008/03/11 09:00
MHDA- 2008/04/23 09:00
CRDT- 2008/03/11 09:00
PHST- 2008/02/21 00:00 [received]
PHST- 2008/02/27 00:00 [accepted]
PHST- 2008/03/11 09:00 [pubmed]
PHST- 2008/04/23 09:00 [medline]
PHST- 2008/03/11 09:00 [entrez]
AID - S0006-291X(08)00408-7 [pii]
AID - 10.1016/j.bbrc.2008.02.120 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 May 9;369(3):939-42. doi: 
      10.1016/j.bbrc.2008.02.120. Epub 2008 Mar 6.