Polymorphic Changes in the 5’ Flanking Region of Factor VII Have a Combined Effect on Promoter Strength
Polymorphic Changes in the 5’ Flanking Region of Factor VII Have a Combined Effect on Promoter Strength
复制标题
因子 VII 5’侧翼区域的多态性变化对启动子强度有综合影响
作者：
R. Kudaravalli;Theresa M. Tidd;M. Pinotti;A. Ratti;R. Santacroce;M. Margaglione;B. Dallapiccola;F. Bernardi;P. Fortina;M. Devoto;E. Pollak
摘要促凝血因子VII(FVII)基因5‘侧翼区的多态差异与FVII凝血活性(FVII：C)和FVII抗原(FVII：Ag)水平的变化有关。位于翻译起始点上游323bp处的十核苷酸插入多态(CCTATATCCT)与每个包含该插入的等位基因FVII：C水平降低约20%相关。然而，十核苷酸多态与位于-122和-401的两个单核苷酸多态(SNPs)的连锁不平衡使得很难准确地确定这些基因变化在降低FVII水平中的功能作用。在体外对HepG2细胞的报告基因研究分析了-401、-323和-122的8个可能的多态位点组合，揭示了存在这三个同时存在的多态变化以最大限度地降低启动子强度的必要性。此外，这些体外结果得到了对89名非洲血统个体的体内研究的支持，其中34%的人表现出一种新的单倍型，该单倍型显示了-323和-401的多态变化，但缺乏-122的变化。
Summary Polymorphic differences in the 5’ flanking region of the gene encoding procoagulant protein Factor VII (FVII) are associated with variations in FVII coagulant activity (FVII:C) and FVII antigen (FVII:Ag) levels. A decanucleotide insert polymorphism (CCTATATCCT) at 323 bp upstream of the start site of translation correlates with a decrease of approximately 20% FVII:C levels per allele containing this insert. However, linkage disequilibrium of the decanucleotide polymorphism with two single nucleotide polymorphisms (SNPs) at –122 and –401 have made it difficult to pinpoint the functional role, if any, of these genetic changes in lowering FVII levels. In vitro reporter gene studies in HepG2 cells analyzing the 8 possible combinations of polymorphic sites at –401, –323, and –122 reveal the necessity of the presence of the three concurrent polymorphic changes to maximally decrease promoter strength. In addition, these in vitro results are supported by in vivo studies in 89 individuals of African heritage, 34% of whom display a new haplotype that shows the polymorphic changes at -323 and -401 but lacks the change at -122.
纤维蛋白原和因子 VIII（而非因子 VII）与老年人亚临床心血管疾病的测量相关。
DOI：
10.1161/01.atv.15.9.1269
发表时间：
1995
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
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作者：
Tracy,RP;Bovill,EG;Yanez,D;Psaty,BM;Fried,LP;Heiss,G;Lee,M;Polak,JF;Savage,PJ
通讯作者：
Savage,PJ