Scopes D, Berg L P, Krawczak M, Kakkar V V, Cooper D N
Charter Molecular Genetics Laboratory, Thrombosis Research Institute, London, UK.
Blood Coagul Fibrinolysis. 1995 Jun;6(4):317-21. doi: 10.1097/00001721-199506000-00004.
The haplotype frequencies of two closely linked diallelic polymorphisms in the protein C(PROC) gene promoter were determined in the British population. In principle, differences in transcription efficiency between PROC promoter haplotypes could represent an additional risk factor in determining whether or not an individual already predisposed to venous thrombosis will come to clinical attention. In order to explore this postulate, transient transfection of human hepatoma cells with PROC promoter-luciferase reporter gene constructs was performed in vitro. In HepG2 cells, the T.....A haplotype exhibited at least a two-fold higher transcription efficiency than the C.....G haplotype. A sample of British protein C deficiency patients with recurrent venous thrombosis was then allelotyped by a combination of oligonucleotide discriminant hybridization and DNA sequencing. The frequency of the low expressing C.....G haplotype was found to be slightly yet not significantly higher in these patients (0.43) than in controls (0.35).
在英国人群中测定了蛋白C（PROC）基因启动子中两个紧密连锁的双等位基因多态性的单倍型频率。原则上，PROC启动子单倍型之间转录效率的差异可能是决定个体是否已经易患静脉血栓形成并因此引起临床关注的一个额外风险因素。为了探究这一假设，在体外用人肝癌细胞进行了PROC启动子-荧光素酶报告基因构建体的瞬时转染。在HepG2细胞中，T.....A单倍型的转录效率比C.....G单倍型至少高两倍。然后通过寡核苷酸鉴别杂交和DNA测序相结合的方法对一组患有复发性静脉血栓形成的英国蛋白C缺乏症患者进行了基因分型。结果发现，低表达的C.....G单倍型在这些患者中的频率（0.43）略高于对照组（0.35），但差异不显著。
