Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene
Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene
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DOI：
10.1016/s0303-7207(01)00406-3
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发表时间：
2001-05
影响因子：
4.1
通讯作者：
G. Whitfield;L. S. Remus;P. Jurutka;H. Zitzer;A. K. Oza;H. Dang;C. Haussler;M. Galligan;Michelle L. T
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文献类型：
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作者：
G. Whitfield;L. S. Remus;P. Jurutka;H. Zitzer;A. K. Oza;H. Dang;C. Haussler;M. Galligan;Michelle L. T
在20个人成纤维细胞系中评价了两个非连锁的人维生素D受体（hVDR）基因多态性的功能意义。确定外显子II中Fok I限制性位点（F/f）和外显子IX中单重（A）重复序列（L/S）的基因型，并使用转染的1，25-二羟维生素D3应答报告基因测量内源性hVDR蛋白的相对转录活性。观察到的活性范围为2-100倍的激素诱导，F和L双等位基因形式显示出更高的活性。只有同时考虑两个位点的基因型时，才出现统计学显著差异。此外，hVDR活性和基因型之间的相关性进一步分离成具有相似基因型分布的明确定义的高活性组和低活性组。这些结果不仅证明了hVDR中F/f和L/S常见多态性的功能相关性，而且还为影响受体效力的第三个遗传变量提供了新的证据。
The functional significance of two unlinked human vitamin D receptor (hVDR) gene polymorphisms was evaluated in twenty human fibroblast cell lines. Genotypes at both a Fok I restriction site (F/f) in exon II and a singlet (A) repeat in exon IX (L/S) were determined, and relative transcription activities of endogenous hVDR proteins were measured using a transfected, 1,25-dihydroxyvitamin D3-responsive reporter gene. Observed activities ranged from 2–100-fold induction by hormone, with higher activity being displayed by the F and the L biallelic forms. Only when genotypes at both sites were considered simultaneously did statistically significant differences emerge. Moreover, the correlation between hVDR activity and genotype segregated further into clearly defined high and low activity groups with similar genotypic distributions. These results not only demonstrate functional relevance for both the F/f and L/S common polymorphisms in hVDR, but also provide novel evidence for a third genetic variable impacting receptor potency.