SynthesisArteriosclerosis, thrombosis, and vascular biology2014
Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.
Synthesis in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Genetic variants in PLG, LPA, and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels.Blood · 2014Pooled it
- Historical review: more than two decades understanding the genetic architecture of hemostasis and thrombosis.Journal of thrombosis and haemostasis : JTH · 2026Review
- A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment.Journal of thrombosis and haemostasis : JTH · 2024Article
- Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.Science (New York, N.Y.) · 2023Article
- Article
- Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.Journal of thrombosis and haemostasis : JTH · 2022Article
- Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.Nature communications · 2022Article
- Coagulation and complement: Key innate defense participants in a seamless web.Frontiers in immunology · 2022Review
- Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits.Genome medicine · 2021Article
- Effects of Thyroid Function on Hemostasis, Coagulation, and Fibrinolysis: A Mendelian Randomization Study.Thyroid : official journal of the American Thyroid Association · 2021Article
- FGL1 as a modulator of plasma D-dimer levels: Exome-wide marker analysis of plasma tPA, PAI-1, and D-dimer.Journal of thrombosis and haemostasis : JTH · 2021Article
- Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis.Neurology · 2021Article
- Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity.The Journal of clinical investigation · 2020Article
- Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults.Genome medicine · 2020Article
- COVID-19 - Toward a comprehensive understanding of the disease.Cardiology journal · 2020Review
- The role of haematological traits in risk of ischaemic stroke and its subtypes.Brain : a journal of neurology · 2020Article
- Article
- Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.NPJ genomic medicine · 2019Article
- Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.PloS one · 2017Article
- Rare variant associations with waist-to-hip ratio in European-American and African-American women from the NHLBI-Exome Sequencing Project.European journal of human genetics : EJHG · 2016Article
Corrections and comments
- Commented on by
- Erratum issuedYamkauchi, Munekazu [corrected to Yamakuchi, Munekazu]
Authors and funding
96 authors at 20 institutions in 10 countries.
Funding
Abstract
objectiveTissue 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
resultsFourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0×10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9×10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3×10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (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 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke.
conclusionsWe identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.