ID 112164
Title Alternative
The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene
Author
Arai, Hidekazu The University of Tokushima
Yoshida, Michiko The University of Tokushima
Yamamoto, Hironori The University of Tokushima KAKEN Search Researchers
Morita, Kyoko The University of Tokushima
Kubota, Megumi Okayama Prefectural University
Yoshida, Shigeko Okayama Prefectural University
Ikeda, Mikiko Okayama Prefectural University
Keywords
vitamin D receptor (VDR)
polymorphism
bone mineral density (BMD)
caudal-related homeodomain Cdx-2
Content Type
Journal Article
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.
Journal Title
Shikoku Acta Medica
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
55
Issue
6
Start Page
225
End Page
231
Sort Key
225
Published Date
1999-12-25
FullText File
language
jpn
TextVersion
Publisher
departments
Medical Sciences