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ID 112164
タイトル別表記
The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene
著者
新井, 英一 徳島大学
芳田, 美智子 徳島大学
森田, 恭子 徳島大学
久保田, 恵 岡山県立大学
吉田, 繁子 岡山県立大学
池田, 己喜子 岡山県立大学
キーワード
vitamin D receptor (VDR)
polymorphism
bone mineral density (BMD)
caudal-related homeodomain Cdx-2
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
四国医学雑誌
ISSN
00373699
cat書誌ID
AN00102041
出版者
徳島医学会
55
6
開始ページ
225
終了ページ
231
並び順
225
発行日
1999-12-25
フルテキストファイル
言語
jpn
著者版フラグ
出版社版
部局
医学系