ID | 112164 |
Title Alternative | The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene
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Author |
Arai, Hidekazu
The University of Tokushima
Yoshida, Michiko
The University of Tokushima
Morita, Kyoko
The University of Tokushima
Miyamoto, Ken-ichi
The University of Tokushima
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Takeda, Eiji
The University of Tokushima
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Kubota, Megumi
Okayama Prefectural University
Yoshida, Shigeko
Okayama Prefectural University
Ikeda, Mikiko
Okayama Prefectural University
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Keywords | vitamin D receptor (VDR)
polymorphism
bone mineral density (BMD)
caudal-related homeodomain Cdx-2
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Content Type |
Journal Article
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Description | The major physiological activity of 1,25-hydroxyvitamin 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 demonstrated that the caudal-related homeodomain Cdx-2 played an important role in the intestine-specific transcription of the human VDR gene. In the present 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 nt relative to the transcription start site of human VDR gene, 5'-A_TAAAAACTTAT'-3'), 82 were genotype Cdx-G (guanine at-3731 nt, 5'-G_TAAAAACTTAT-3'), 131 were genotype Cdx-A/G (heterozygote). The bone mineral density (BMD) in the lumbar spine (L2-4) with the Cdx-A homozygote was 12% lower than that with the Cdx-G homozygote (P<0.05). In electropholertic gel mobility shift assay, 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.
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Journal Title |
Shikoku Acta Medica
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ISSN | 00373699
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NCID | AN00102041
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Publisher | 徳島医学会
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Volume | 55
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Issue | 6
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Start Page | 225
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End Page | 231
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Sort Key | 225
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Published Date | 1999-12-25
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FullText File | |
language |
jpn
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TextVersion |
Publisher
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departments |
Medical Sciences
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