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

维生素D受体基因Fok-I多态性对青年血清25-羟维生素D和骨特异性碱性磷酸酶以及跟骨定量超声参数的影响

Rieko Tanabe ； Yuka Kawamura ； Naoko Tsugawa ； Mayu Haraikawa ； Natsuko Sogabe ； Toshio Okano ； Takayuki Hosoi ； Masae Goseki-Sone

《Asia Pacific Journal of Clinical Nutrition》 24卷2期 (2015/06) Pp. 329-335

https://doi.org/10.6133/apjcn.2015.24.2.01

摘要

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）VDRFok-I基因型对血清中骨特异性碱性磷酸酶（ALP）、25-羟基维生素D_3[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VDRFok-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。

關鍵字

维生素D受体Fok-I基因多态性 ； 骨特异性碱性磷酸酶 ； 25-羟基维生素D_3 ； 1-α,25-二羟基维生素D_3 ； 定量超声

並列摘要

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 D_3 [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.

並列關鍵字

vitamin D receptor Fok-I polymorphism ； bone-specific alkaline phosphatase ； 25-hydroxyvitamin D3 ； 1-alpha ； 25- dihydroxyvitamin D3 ； quantitative ultrasound