| RRC ID |
41403
|
| 著者 |
Arai H, Miyamoto KI, Yoshida M, Yamamoto H, Taketani Y, Morita K, Kubota M, Yoshida S, Ikeda M, Watabe F, Kanemasa Y, Takeda E.
|
| タイトル |
The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene.
|
| ジャーナル |
J Bone Miner Res
|
| Abstract |
The major physiological activity of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the regulation of calcium absorption in the small intestine, and the level of vitamin D receptor (VDR) is an important factor in this regulation. In a previous study, we indicated-that the caudal-related homeodomain Cdx-2 played an important role in the intestine-specific transcription of the human VDR gene. In this study, the polymorphism was identified in the core sequence 5'-ATAAAAACTTAT-3' in the Cdx-2 binding site in the VDR gene promoter. In 261 Japanese women with genotyped VDR polymorphisms, 48 were genotype Cdx-A (adenine at -3731 nucleotides [nt] relative to the transcription start site of human VDR gene 5-ATAAAAACTTAT), 82 were genotype Cdx-G (guanine at -3731 nt, 5'-GTAAAAACTTAT-3'), and 131 were genotype Cdx-A/G (heterozygote). In postmenopausal Japanese women, the bone mineral density (BMD) in the lumbar spine (L2-L4) with the Cdx-G homozygote was 12% lower than that with the Cdx-A homozygote (p < 0.05). In electrophoretic gel mobility shift assay (EMSA), the oligonucleotide with Cdx-G allele markedly decreased the binding to Cdx-2 compared with that in the Cdx-A allele. The transcriptional activity of the VDR promoter with Cdx-G allele was decreased to 70% of the Cdx-A allele. In addition, in the herpes simplex virus thymidine kinase promoter, the Cdx-2 binding element with the G allele showed significantly lower transcriptional activity than that of the A allele. Thus, the polymorphism in the Cdx-2 binding site of the VDR gene (Cdx-polymorphism) would affect the expression of VDR in the small intestine. In addition, this polymorphism may modulate BMD in postmenopausal Japanese women.
|
| 巻・号 |
16(7)
|
| ページ |
1256-64
|
| 公開日 |
2001-7-1
|
| DOI |
10.1359/jbmr.2001.16.7.1256
|
| PMID |
11450701
|
| MeSH |
Adult
Aged
Alleles
Animals
Base Sequence
Binding Sites
Bone Density / genetics
CDX2 Transcription Factor
COS Cells
Electrophoretic Mobility Shift Assay
Female
Gene Expression Regulation
Genotype
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Japan
Menopause
Middle Aged
Osteoporosis, Postmenopausal / genetics
Polymorphism, Genetic / genetics*
Promoter Regions, Genetic / genetics
Receptors, Calcitriol / genetics*
Response Elements / genetics*
Spine / physiology
Trans-Activators
Transfection
Tumor Cells, Cultured
|
| IF |
5.854
|
| 引用数 |
193
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
