کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10764865 | 1050567 | 2010 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Functional characterization of polymorphisms in the human TFPI gene
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Tissue factor pathway inhibitor (TFPI) is the primary physiological inhibitor of tissue factor (TF) induced coagulation. Low plasma TFPI levels have been shown to be associated with increased risk of arterial and venous thrombosis. Several clinical studies have reported that single nucleotide polymorphisms (SNPs) in the regulatory regions of the gene, such as the â287T/C, the â399C/T, and the â33T/C SNPs, may affect plasma TFPI levels. However, molecular studies investigating the functionality of the polymorphisms are lacking. In this study, we found that the â287C and â399T alleles affected the activity of the promoter using a reporter gene system. This was also the case for the â33T/C polymorphism. An association regarding the transcriptional activity of the reporter gene was detected between the â287C allele and the â33T/C polymorphism. Analysis of the polymorphic sites with electrophoretic mobility shift assay (EMSA) showed that all three polymorphisms potentially alter DNA-protein interactions. Based on these findings, we speculate that the â287C and the â33C alleles can be associated with lowered risk of thrombosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 397, Issue 1, 18 June 2010, Pages 106-111
Journal: Biochemical and Biophysical Research Communications - Volume 397, Issue 1, 18 June 2010, Pages 106-111
نویسندگان
Grethe Skretting, Benedicte Stavik, Nina E. Landvik, Christiane F. Myklebust, Nina Iversen, Shan Zienolddiny, Per Morten Sandset,