Abstract
Using a large-scale representative sample of the Japanese female population, we examined the effects of a single nucleotide polymorphism within a binding site of Cdx-2 in the promoter region of the vitamin D receptor gene on bone mineral density (BMD), and the interactions between this polymorphism and lifestyle factors on BMD. Fifty women were randomly selected from each of the 5-year age-stratified populations (15–79 years) in each of three chosen municipalities as a part of the Japanese Population-based Osteoporosis Study. BMD at the lumbar spine, hip, and distal forearm was measured using dual-energy X-ray absorptiometry at baseline and again in a follow-up study conducted 3 years later. Information on lifestyle factors was collected in a questionnaire and followed up in interviews. The G-to-A polymorphism within the Cdx-2 binding site was determined by a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. The baseline BMD in the ultradistal forearm in premenopausal women with the GG genotype was significantly lower than in those with other genotypes. There was no association between the Cdx-2 genotype and the change in BMD at any of the skeletal sites. We found significant associations between daily milk consumption and baseline BMD at some skeletal sites but only in subjects with the GG genotype. In conclusion, the Cdx-2 polymorphism alone did not have a substantial effect on BMD in Japanese women. However, this polymorphism might have some effect in women with low calcium intake.
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Acknowledgments
This study was conducted by the JPOS Study Group, comprising Takashi Akiba (Tokyo Medical and Dental University), Etsuko Kajita (Nagoya University), Harumi Nishino (Toyama Institute of Health), Tomoharu Matsukura (Kanazawa University), Toshio Matsumoto (Tokushima University), Yuho Sato (Tenshi College), and Takashi Yamagami (Hokuriku Health Service Association), in addition to the authors, who have obtained financial support from the Japan Milk Promotion Board and the Japan Dairy Council. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and grants from the Japan Society for the Promotion of Science (A#11770211, B#10470114, C#12204105, 1998–2000) and from the Research Society for Metabolic Bone Disease (1999–2001). The authors express their special thanks to the personnel of the health departments of the three municipalities investigated for their excellent support of the study.
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Morita, A., Iki, M., Dohi, Y. et al. Effects of the Cdx-2 Polymorphism of the Vitamin D Receptor Gene and Lifestyle Factors on Bone Mineral Density in a Representative Sample of Japanese Women: The Japanese Population-based Osteoporosis (JPOS) Study. Calcif Tissue Int 77, 339–347 (2005). https://doi.org/10.1007/s00223-005-0047-2
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DOI: https://doi.org/10.1007/s00223-005-0047-2