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

Abstract

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 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 +/- 0.02 vs 2.35 +/- 0.01 mmol/l) and higher 1,25-dihydroxyvitamin D (95 +/- 4.8 vs. 76 +/- 3.8 pmol/l). Further discrimination of the genotype was achieved using two additional RFLPs (ApaI, A and TaqI, 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.

Vitamin D receptor gene <em>Taq</em>I and <em>Apa</em>l polymorphisms and steroid responsiveness in childhood idiopathic nephrotic syndrome

“…Many previous studies on the effect of VDR gene polymorphism on renal diseases showed conflicting results. 9,11,12 No effects of the different VDR polymorphic genotypes on both chronic kidney disease and end-stage renal disease were previously documented, [20][21][22][23][24][25] whereas studies on systemic lupus erythematosus nephritis, including secondary nephrotic syndrome with or without renal dysfunction, reported an association of renal involvement with the bb genotype of BsmI polymorphism, which is a common single-nucleotide polymorphism of the VDR gene. 19 INS has been widely considered to be a primary immune disease associated with immune regulatory imbalance between Th1 and Th2 cytokines, which are thought to play major roles in the pathogenesis and progression of the disease .…”

“…10 Ethnic and genetic differences in the frequencies of the VDR polymorphic genotypes have been previously reported in different populations. 9,11,12 In this study, we explore the frequency of VDR gene TaqI and ApaI restriction fragment length polymorphisms (RFLPs) in Kuwaiti Arab children with INS and the effect of the different VDR polymorphic genotypes on steroid responsiveness.…”

Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese

“…Genotype was determined from the lengths of fragments, i.e. BB, Bb, and bb (PCR-restriction-fragmentsof-length-polymorphism method) [22].…”

Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia

“…4 Several single nucleotide polymorphisms (SNPs) have been shown to influence BMD in adults, especially those of the vitamin-D receptor gene (VDR). [7][8][9][10][11][12] The extent of the influence of VDR SNPs on BMD may be dependent on age and menopausal state. 13 In healthy children, only a few studies on the influence of VDR 3'-end SNPs (BsmI, ApaI, TaqI) on BMD have been reported, with conflicting results.…”