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Vitamin D Receptor Alleles, Bone Mineral Density And Turnover In Premenopausal Japanese Women

Akifumi Tokitan, H. Matsumoto, N. Morrison, T. Tawa, Y. Miura, K. Fukamauchi, N. Mitsuhashi, M. Irimoto, Syunji Yamamori, M. Miura, Takako Watanabe, Y. Kuwabara, K. Yabuta, J. Eisman
Published 1996 · Biology, Medicine

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Recent studies have shown that genetic effects on bone mineral density (BMD) and bone turnover are related to allelic variation in the vitamin D receptor (VDR) gene. We examined allelic influences of the VDR gene on bone turnover and density in 202 normal healthy premenopausal Japanese women (age 30.1 ± 1.2, mean ± SEM). The VDR effect on BMD and turnover is similar to that observed in Caucasian women; however, there are major differences in allele frequency. The B allele by Bsm I restriction fragment length polymorphisms (RFLPs), associated with low BMD and high bone turnover, is found in only 12% of Japanese women (1.4% homozygote BB), compared with 41% of Caucasians (16.7% homozygote BB). In comparing the two most frequent genotypes, Bb heterozygotes (21.5%) and bb homozygotes (77.1%), BMD is 5.3% lower in Bb heterozygotes, and levels of bone formation markers including osteocalcin and bone‐specific alkaline phosphatase are 20–32% higher with lower serum calcium (2.30 ± 0.02 vs 2.35 ± 0.01 mmol/1) and higher 1,25‐dihydroxyvitamin D (95 ± 4.8 vs. 76 ± 3.8 pmol/1). Further discrimination of the genotype was achieved using two additional RFLPs (Apa I, A and Taq I, T); the lumbar spine BMD of the common genotype BbAATt was 9.3% (0.94 SD) lower than in the bbaaTT genotype in premenopausal Japanese women. These data confirm that VDR RFLPs affect bone mineral metabolism regardless of racial differences. Moreover, the VDR genotypes based on haplotype analysis should yield useful insights into the potential prevention of osteoporosis. (J Bone Miner Res 1996;11:1003‐1009)
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