Vitamin D receptor gene haplotype is associated with body height and bone size
Vitamin D receptor gene haplotype is associated with body height and bone size
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DOI：
10.1210/jc.2006-1134
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发表时间：
2007-04-01
影响因子：
5.8
通讯作者：
Uitterlinden, Andre G.
中科院分区：
文献类型：
--
作者：
Fang, Yue;van Meurs, Joyce B. J.;Uitterlinden, Andre G.
背景：成人身高是一种复杂的遗传特征。维生素 D 内分泌系统对多种生理过程，尤其是骨骼代谢具有多效作用。我们最近鉴定了影响维生素 D 受体 (VDR) mRNA 表达的启动子和 3'-非翻译区 (UTR) 单倍型等位基因。 目的：我们研究 VDR 基因变异是否会导致身高遗传变异。 设计和受试者：我们研究了两个独立群体 (n = 7187) 的 VDR 单倍型等位基因和身高。在一项荟萃分析中（n = 14,157，来自 27 项研究和我们当前的数据），我们评估了 Bsm I 多态性的影响。 结果：连锁不平衡区块 3 和区块 5 的单倍型与身高差异相关，鹿特丹研究 (P = 0.00002) 和阿姆斯特丹纵向衰老研究 (P = 0.001) 中的累加效应证据。极端基因型之间的身高差异分别为 1.4 和 2.7 厘米。这种关系与年龄、性别、椎骨骨折的存在以及与年龄相关的身高下降无关。在鹿特丹人群中，我们发现组合基因型与椎骨面积减小（P = 0.03）和股骨颈宽度缩小（P = 0.002）相关。在荟萃分析中，“BB”基因型受试者比“bb”基因型受试者高 0.6 厘米（95% 置信区间，0.2-1.1 厘米）（P = 0.006）。 结论：我们的研究和荟萃分析证明，VDR 基因变异与身高差异相关。仍有待进一步研究来确认这种关联的潜在机制是否涉及对确定骨大小很重要的细胞中较低的 VDR 表达。
Context: Adult stature is a complex genetic trait. The vitamin D endocrine system has pleiotropic effects on several physiological processes, especially on skeletal metabolism. We recently identified promoter and 3'-untranslated region (UTR) haplotype alleles that influence vitamin D receptor (VDR) mRNA expression.Objective: We studied whether VDR gene variants contribute to the genetic variation in height.Design and Subjects: We studied VDR haplotype alleles and body height in two independent populations (n = 7187). In a meta-analysis (n = 14,157 from 27 studies and our current data), we evaluated the effect of the Bsm I polymorphism.Results: Haplotypes of the linkage disequilibrium block 3 and block 5 were associated with body height differences with evidence for additive effects in the Rotterdam Study (P = 0.00002) and the Longitudinal Aging Study Amsterdam study (P = 0.001). Height differences between the extreme genotypes were 1.4 and 2.7 cm, respectively. The relationship was independent of age, gender, presence of vertebral fractures, and age-related height loss. In the Rotterdam population, we found the combined genotype to be associated with decreased vertebral area (P = 0.03) and femoral narrow neck width (P = 0.002). In the meta-analysis, subjects with the "BB" genotype were 0.6 cm (95% confidence interval, 0.2-1.1 cm) taller than those with the "bb" genotype (P = 0.006).Conclusion: VDR gene variants are associated with differences in body height as evidenced by our study and by a meta-analysis. It remains for further studies to confirm whether the underlying mechanism of the association involves lower VDR expression in cells important for determining bone size.