New Functional Promoter Polymorphism, CETP/−629, in Cholesteryl Ester Transfer Protein (CETP) Gene Related to CETP Mass and High Density Lipoprotein Cholesterol Levels
New Functional Promoter Polymorphism, CETP/−629, in Cholesteryl Ester Transfer Protein (CETP) Gene Related to CETP Mass and High Density Lipoprotein Cholesterol Levels
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胆固醇酯转移蛋白 (CETP) 基因中与 CETP 质量和高密度脂蛋白胆固醇水平相关的新功能启动子多态性 CETP/−629
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
MustaphaRouis
中科院分区：
文献类型：
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作者：
ChristianeDachet;OdettePoirier;FrançoisCambien;JohnChapman;MustaphaRouis
摘要-描述了位于胆固醇酯转运蛋白（CETP）基因启动子-629位点（CETP/-629A/C）的一种新多态性。在来自ECTIM研究的536名对照受试者样本中，与C等位基因相比，− 629 A等位基因与较低的CETP质量（P <0.0001）和较高的高密度脂蛋白胆固醇（P<0.001）相关。在HepG 2细胞中，使用荧光素酶表达载体进行转染研究，该载体包含CETP启动子的777 bp片段，并在-629位含有A或C，结果显示A等位基因启动子片段的荧光素酶活性显著降低（-25%，P<0.05）。通过凝胶迁移分析，DNA-蛋白质的相互作用进行了评估，在HepG 2细胞核提取物中使用2个探针（A或C探针）组成的20 bp的启动子序列周围的多态性位点。用A和C探针鉴定了两种具有不同迁移速率的特异性复合物。竞争与过量的寡核苷酸含有Sp1的共识结合位点…
Abstract—A new polymorphism located at position −629 (CETP/−629A/C) in the promoter of the cholesteryl ester transfer protein (CETP) gene is described. The −629A allele was associated with lower CETP mass (P<0.0001) and higher high density lipoprotein cholesterol (P<0.001) than the C allele in a sample of 536 control subjects from the ECTIM study. Transfection studies in HepG2 cells with a luciferase expression vector incorporating a 777-bp fragment of the CETP promoter and containing either A or C at position −629 showed significantly lower luciferase activity with the promoter fragment of the A allele (−25%, P<0.05). By gel-shift assay, DNA-protein interactions were evaluated in nuclear extracts of HepG2 cells with the use of 2 probes (A or C probe) composed of 20 bp of the promoter sequence surrounding the polymorphic site. Two specific complexes of distinct migration rate were identified with the A and the C probe. Competition with an excess of oligonucleotide containing the Sp1 consensus binding site...