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Vitamin D receptor alleles, bone mineral density and turnover in premenopausal Japanese women

✍ Scribed by Dr. Akifumi Tokitan; Hiroshi Matsumoto; Nigel A. Morrison; Toshiya Tawa; Yuko Miura; Kazutaka Fukamauchi; Naoki Mitsuhashi; Masahiro Irimoto; Syunji Yamamori; Masakazu Miura; Takako Watanabe; Yoshihiro Kuwabara; Keijiro Yabuta; John A. Eisman

Publisher: American Society for Bone and Mineral Research
Year: 2009
Tongue: English
Weight: 625 KB
Volume: 11
Category: Article
ISSN: 0884-0431
DOI: 10.1002/jbmr.5650110718

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✦ Synopsis

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 O R ) gene. We examined allelic influences of the VDR gene on bone turnover and density in 202 normal healthy premenopausal Japanese women (age 30.1 f 1.2, mean -C 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 BsmI 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 2 0.02 vs 2.35 f 0.01 mmol/l) and higher 1,25-dihydroxyvitamin D (95 -C 4.8 vs. 76 -C 3.8 pmoM). Further discrimination of the genotype was achieved using two additional R n P s (ApuI, A and TuqI, 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 R n P s 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. (

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