Abstract | BACKGROUND: METHODS: In an analysis of 15 patients and 60 normal subjects, we detected 14 polymorphisms and nine haplotypes in the regulatory region. We classified the 4-kbp regulatory region of the patients into: the TATA box including A(TA)7TAA; a phenobarbital responsive enhancer module including c.-3275T>G; and a region including other ten linked polymorphisms. The effect on transcription of these polymorphisms was studied. RESULTS: All haplotypes with A(TA)7TAA had c.-3275T>G and additional polymorphisms. In an in-vitro expression study of the 4-kbp regulatory region, A(TA)7TAA alone did not significantly reduce transcription. In contrast, c.-3275T>G reduced transcription to 69% of that of wild type, and the linked polymorphisms reduced transcription to 88% of wild type. Transcription of the typical regulatory region of the patients was 56% of wild type. Co-expression of constitutive androstane receptor (CAR) increased the transcription of wild type by a factor of 4.3. Each polymorphism by itself did not reduce transcription to the level of the patients, however, even in the presence of CAR. CONCLUSIONS: These results imply that co-operation of A(TA)7TAA, c.-3275T>G and the linked polymorphisms is necessary in causing Gilbert syndrome.
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Authors | Katsuyuki Matsui, Yoshihiro Maruo, Hiroshi Sato, Yoshihiro Takeuchi |
Journal | BMC gastroenterology
(BMC Gastroenterol)
Vol. 10
Pg. 57
(Jun 08 2010)
ISSN: 1471-230X [Electronic] England |
PMID | 20529348
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Constitutive Androstane Receptor
- Receptors, Cytoplasmic and Nuclear
- UGT1A1 enzyme
- Glucuronosyltransferase
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Topics |
- Asian People
(genetics)
- Case-Control Studies
- Constitutive Androstane Receptor
- Gilbert Disease
(genetics, metabolism)
- Glucuronosyltransferase
(genetics)
- Haplotypes
(genetics)
- Humans
- Japan
- Polymorphism, Genetic
(genetics)
- Receptors, Cytoplasmic and Nuclear
(metabolism)
- Transcription, Genetic
- White People
(genetics)
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