English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Objective— Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA. Approach and Results— Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P &lt;5.0×10−8 ). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599;P =2.9×10−14 ) withinSTXBP5 . The second locus is on 8p11.21. The lead SNP (rs3136739;P =1.3×10−9 ) is intronic toPOLB and &lt;200 kb away from the tPA encoding the genePLAT . We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r 2 =0.50) within exon 5 ofPLAT (P =2.0×10−8 ). The third locus is on 12q24.33, with the lead SNP (rs7301826;P =1.0×10−9 ) within intron 7 ofSTX2 . We further found evidence for the association of lead SNPs inSTXBP5 andSTX2 with expression levels of the respective transcripts. In in vitro cell studies, silencingSTXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencingSTX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke.Conclusions— We identified 3 loci associated with circulating tPA levels, thePLAT region,STXBP5 , andSTX2. Our functional studies implicate a novel role forSTXBP5 andSTX2 in regulating tPA release.

arteriosclerosis, thrombosis, and vascular biology

Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial <i>STXBP5</i> and <i>STX2</i>

Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2