The Polymorphism in the Caudal-Related Homeodomain Protein Cdx-2 Binding Element in the Human Vitamin D Receptor Gene
Open Access
- 1 July 2001
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 16 (7), 1256-1264
- https://doi.org/10.1359/jbmr.2001.16.7.1256
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.Keywords
This publication has 39 references indexed in Scilit:
- Vitamin D Receptor Gene Fok1 Polymorphism Predicts Calcium Absorption and Bone Mineral Density in ChildrenJournal of Bone and Mineral Research, 1999
- Vitamin D Receptor Gene Start Codon Polymorphisms (FokI) and Bone Mineral Density: Interaction with Age, Dietary Calcium, and 3′-End Region PolymorphismsJournal of Bone and Mineral Research, 1998
- Lack of Correlation Between Start Codon Polymorphism of the Vitamin D Receptor Gene and Bone Mineral Density in Premenopausal French Women: The OFELY StudyJournal of Bone and Mineral Research, 1998
- The Vitamin D Receptor Start Codon Polymorphism (FokI) and Bone Mineral Density in Premenopausal American Black and White WomenJournal of Bone and Mineral Research, 1997
- The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal mexican-American womenJournal of Bone and Mineral Research, 1996
- Vitamin D receptor gene polymorphisms are not related to bone turnover, rate of bone loss, and bone mass in postmenopausal women: The OFELY studyJournal of Bone and Mineral Research, 1996
- Alterations in mRNA expression of duodenal 1,25-dihydroxyvitamin D3 receptor and vitamin D-dependent calcium binding protein in aged wistar ratsExperimental Gerontology, 1994
- Two intestinal specific nuclear factors binding to the lactase‐phlorizin hydrolase and sucrase‐isomaltase promoters are functionally related oligomeric moleculesFEBS Letters, 1994
- Dietary restriction of calcium, phosphorus, and vitamin D elicits differential regulation of the mrnas for avian intestinal calbindin-D28K and the 1,25-dihydroxyvitamin D3 receptorJournal of Bone and Mineral Research, 1992
- Effects of age and estrogen on calcium absorption in the ratJournal of Bone and Mineral Research, 1986