| RRC ID |
68507
|
| 著者 |
Uno Y, Sakamoto Y, Yoshida K, Hasegawa T, Hasegawa Y, Koshino T, Inoue I.
|
| タイトル |
Characterization of six base pair deletion in the putative HNF1-binding site of human PXR promoter.
|
| ジャーナル |
J Hum Genet
|
| Abstract |
Pregnane X receptor (PXR) regulates transcription of drug metabolism genes such as CYP3A4 and MDR1. Several species of PXR transcripts have been reported, including hPAR-2 with an extended amino-terminus. Database search identified a 6-bp deletion at the putative HNF1 binding element on the proximal region flanking to the hPAR-2 transcription start site. Aspirin-induced asthma (AIA) is a typical drug-induced phenotype due to aspirin or nonsteroidal antiinflammatory drugs, and these drugs are metabolized by CYP2C9 and UGT1A6, which are regulated by PXR. We examined a possible association between the 6-bp deletion variant and AIA; 129 AIA patients and 117 controls were genotyped, and no allelic association was observed. Characterization of the hPAR-2 promoter revealed that the proximal region of 1.5-kb from the transcription start site conferred a promoter activity and that the 6-bp deletion diminished the activity. These results suggest that the putative HNF1 binding element is essential for the transcriptional activity of hPAR-2 and also, that substantial numbers of Japanese are in a deficient state. Because of the biological significance of the 6-bp deletion of PXR, the variant might potentially associate with as yet unknown phenotype.
|
| 巻・号 |
48(11)
|
| ページ |
594-7
|
| 公開日 |
2003-1-1
|
| DOI |
10.1007/s10038-003-0076-5
|
| PMID |
14586772
|
| MeSH |
Anti-Inflammatory Agents, Non-Steroidal
Aspirin
Asthma / chemically induced
Asthma / genetics*
Base Pairing
Binding Sites
DNA
DNA-Binding Proteins / metabolism
Hepatocyte Nuclear Factor 1
Hepatocyte Nuclear Factor 1-alpha
Humans
In Vitro Techniques
Middle Aged
Nuclear Proteins / metabolism
Pregnane X Receptor
Receptors, Cytoplasmic and Nuclear / genetics*
Receptors, Cytoplasmic and Nuclear / metabolism
Receptors, Steroid / genetics*
Receptors, Steroid / metabolism
Sequence Deletion*
Transcription Factors / metabolism
|
| IF |
2.831
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2 |
