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Title: Effects of Fok-I polymorphism in vitamin D receptor gene on serum 25-hydroxyvitamin D, bone-specific alkaline phosphatase and calcaneal quantitative ultrasound parameters in young adults.
Author: Tanabe R, Kawamura Y, Tsugawa N, Haraikawa M, Sogabe N, Okano T, Hosoi T, Goseki-Sone M.
Journal: Asia Pac J Clin Nutr; 2015; 24(2):329-35. PubMed ID: 26078251.
Abstract:
Several genes have been implicated as genetic determinants of osteoporosis. Vitamin D receptor (VDR) is an intracellular hormone receptor that specifically binds to the biologically active form of vitamin D, 1-alpha, 25- dihydroxyvitamin D3 [1, 25(OH)2D], and mediates its effects. One of the most frequently studied single nucleotide polymorphisms is the restriction fragment length polymorphism (RFLP) Fok-I (rs2228570). The presence of a Fok-I site, designated f, allows protein translation to initiate from the first ATG. An allele lacking the site (ATG>ACG: designated F), initiates from a second ATG site. In the present study, we explored the effect of the VDR Fok-I genotype on associations among serum bone-specific alkaline phosphatase (ALP), 25- hydroxyvitamin D3 [25(OH)D], 1, 25(OH)2D, and the dietary nutrient intake in healthy young Japanese subjects (n=193). Dietary nutrient intakes were calculated based on 3-day food records before the day of blood examinations. Quantitative ultrasound (QUS) parameters at the right calcaneus (heel bone) were measured. The allele frequencies were 0.622 for the F allele and 0.378 for the f allele in all subjects. Grouped by the VDR genotype, a significant positive correlation between the levels of serum bone-specific ALP and 25(OH)D was observed in the FF-type (p=0.005), but not in the ff-type. In addition, there was a significant positive correlation between the level of serum 25(OH)D and osteo-sono assessment index (OSI) in the FF-type (p=0.008), but not in the ff-type. These results suggest that the level of circulating 25(OH)D is an important factor when assessing the VDR Fok-I polymorphism to prevent osteoporosis. 一些基因已经被证实为骨质疏松症的基因决定性因素。维生素D 受体（VDR）是一种细胞内的激素受体，它可以特异性地与活性状态的维生素D，1-α, 25-二羟基维生素D3 [1,25(OH)2D] 结合，并且调节它的作用。研究最多的单核苷酸多态性是限制性片段长度多态性（RFLP）Fok-I（rs2228570）。在Fok-I 上一个位点，被定为f，使蛋白质转录从第一个ATG 开始。一个等位基因缺失位点 ATG>ACG：定为F，转录是从第二个ATG 开始。本研究探究了健康日本青年人群中（n=193）VDR Fok-I 基因型对血清中骨特异性碱性磷酸酶（ALP）、25- 羟基维生素D3[25(OH)D]、1,25(OH)2D 以及饮食中营养物的摄入之间的影响。饮食中营养素的摄入是根据验血前3 天的饮食记录计算的。定量超声（QUS）参数通过右侧跟骨测得。在整个样本中，F 等位基因频率为0.622，f 等位基因频率为0.378。根据VCR 基因型分组，在FF 基因型组发现血清中骨特异性 ALP 的水平与25(OH)D 有显著正相关（p=0.005），但未在ff 基因型组中发现。同时在FF 基因型组中发现血清中25(OH)D 水平与骨超声评价指数（OSI）显著正相关（p=0.008），但未在ff 基因型组发现。这些结果表明，当评估 VDR Fok-I 多态性时血液中25(OH)D 的水平是预防骨质疏松的一个重要因素。.

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