Identification of Eight Novel Single-Nucleotide Polymorphisms at Human Tissue-type Plasminogen Activator (t-PA) Locus: Association with Vascular t-PA Release In Vivo

Per Ladenvall; Ulrika Wall; Sverker Jern; Christina Jern

doi:10.1055/s-0037-1613990

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2000; 84(02): 150-155
DOI: 10.1055/s-0037-1613990

Rapid Communications

Schattauer GmbH

Identification of Eight Novel Single-Nucleotide Polymorphisms at Human Tissue-type Plasminogen Activator (t-PA) Locus: Association with Vascular t-PA Release In Vivo

Autoren

Per Ladenvall

¹From the Heart and Lung Institute, Clinical Experimental Research Laboratory, Göteborg, Sweden
Ulrika Wall

¹From the Heart and Lung Institute, Clinical Experimental Research Laboratory, Göteborg, Sweden
Sverker Jern

¹From the Heart and Lung Institute, Clinical Experimental Research Laboratory, Göteborg, Sweden
Christina Jern

¹From the Heart and Lung Institute, Clinical Experimental Research Laboratory, Göteborg, Sweden

²Institute of Clinical Neuroscience, Department of Neurology, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden

Abstract

Summary

Recently, we reported that an Alu insertion polymorphism of the tissue-type plasminogen activator (t-PA) gene is associated with vascular t-PA release rates in man. In the current study we searched the t-PA gene for putative functional genetic variants in linkage disequilibrium (LD) with this polymorphism. Healthy individuals with different Alu genotypes and contrasting t-PA release rates were studied. Regulatory and coding regions of the t-PA gene were sequenced. Eight singlenucleotide polymorphisms (SNPs) were identified. Three of these were in significant LD with the Alu polymorphism and consequently associated with t-PA release rates; one in the far upstream enhancer, one in exon 6, and one in intron 10. The enhancer SNP resides within a GC box. Electrophoretic mobility shift assay (EMSA) revealed a reduced binding affinity of Sp1 to the T allele, which is the allele associated with a low t-PA release rate. Variations in exon 6 and intron 10 were silent and without apparent effect on splicing, respectively.

Keywords

Tissue-type plasminogen activator - genetics - single-nucleotide polymorphism (SNP) - enhancer - Sp1

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Referenzen

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