Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.
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- Authors
- Huang, Jie; Sabater-Lleal, Maria; Asselbergs, Folkert W; Tregouet, David; Shin, So-Youn; Ding, Jingzhong; Baumert, Jens; Oudot-Mellakh, Tiphaine; Folkersen, Lasse; Johnson, Andrew D; Smith, Nicholas L; Williams, Scott M; Ikram, Mohammad A; Kleber, Marcus E; Becker, Diane M; Truong, Vinh; Mychaleckyj, Josyf C; Tang, Weihong; Yang, Qiong; Sennblad, Bengt; Moore, Jason H; Williams, Frances M K; Dehghan, Abbas; Silbernagel, GΓΌnther; Schrijvers, Elisabeth M C; Smith, Shelly; Karakas, Mahir; Tofler, Geoffrey H; Silveira, Angela; Navis, Gerjan J; Lohman, Kurt; Chen, Ming-Huei; Peters, Annette; Goel, Anuj; Hopewell, Jemma C; Chambers, John C; Saleheen, Danish; Lundmark, Per; Psaty, Bruce M; Strawbridge, Rona J; Boehm, Bernhard O; Carter, Angela M; Meisinger, Christa; Peden, John F; Bis, Joshua C; McKnight, Barbara; Γhrvik, John; Taylor, Kent; Franzosi, Maria Grazia; Seedorf, Udo; Collins, Rory; Franco-Cereceda, Anders; SyvΓ€nen, Ann-Christine; Goodall, Alison H; Yanek, Lisa R; Cushman, Mary; MΓΌller-Nurasyid, Martina; Folsom, Aaron R; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H; Kooner, Jaspal S; Hofman, Albert; Danesh, John; Clarke, Robert; Meigs, James B; DIAGRAM Consortium; Kathiresan, Sekar; Reilly, Muredach P; CARDIoGRAM Consortium; Klopp, Norman; Harris, Tamara B; Winkelmann, Bernhard R; Grant, Peter J; Hillege, Hans L; Watkins, Hugh; C4D Consortium; Spector, Timothy D; Becker, Lewis C; Tracy, Russell P; MΓ€rz, Winfried; Uitterlinden, Andre G; Eriksson, Per; Cambien, Francois; CARDIOGENICS Consortium; Morange, Pierre-Emmanuel; Koenig, Wolfgang; Soranzo, Nicole; van der Harst, Pim; Liu, Yongmei; O'Donnell, Christopher J; Hamsten, Anders
- Year
- 2012
- Journal
- Blood
- PMID
- 22990020
- DOI
- 10.1182/blood-2012-06-436188
- PMCID
- PMC3520624
We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 Γ 10(-8)) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 Γ 10(-10)); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 Γ 10(-8)); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 Γ 10(-8)). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1.
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|---|---|---|
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Genome-wide identification of loci associated with plasma coagulation factor IX activity. | Han J et al. | β | 2026 | β |
| Historical review: more than two decades understanding the genetic architecture of hemostasis and thrombosis. | Sabater-Lleal M et al. | β | 2026 | β |
| A Contemporary Review of Plasminogen Activator Inhibitor Type 1: Structure, Function, Genetic Architecture, and Intracellular/Extracellular Roles. | Wortley J et al. | β | 2025 | β |
| BMAL1 in Ischemic Heart Disease: A Narrative Review from Molecular Clock to Myocardial Pathology. | Yang J et al. | β | 2025 | β |
| Genome-wide meta-analysis of heavy menstrual bleeding reveals 36 risk loci. | Thibord F et al. | β | 2025 | β |
| Identification of preventive biomarkers associated with circadian rhythms in traumatic brain injury-mediated depression: Expression of SERPINE1 protein and bioinformatics analysis. | Cai Y et al. | β | 2025 | β |
| Integrated single-cell and bulk RNA-sequencing data reveal prognosis and therapeutic response in low-grade glioma based on hypoxia-lactylation related genes. | Tang H et al. | β | 2025 | β |
| Liver steatosis is positively associated with plasminogen activator inhibitor-1 in apparently healthy individuals with overweight and obesity: A FibroScan-Based Cross-Sectional study. | Lisco G et al. | β | 2025 | β |
| Research Progress of BMAL1 in Heart Failure. | Chen F et al. | β | 2025 | β |
| The Antifibrotic Effects of Plasminogen Activator Inhibitor-1 Antagonists are Observed in Rats with Epidural Fibrosis. | Bektasoglu PK et al. | β | 2025 | β |
| The association between clock gene polymorphisms and type 2 diabetes: A systematic review and meta-analysis. | Joshi D et al. | β | 2025 | β |
| The effects of coagulation factors on the risk of Alzheimer's disease: A Mendelian randomization study. | Shi W et al. | β | 2025 | β |
| Variants in candidate genes and their interactions with smoking on the risk of acute coronary syndrome | Franco L et al. | β | 2025 | β |
| A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment. | Gallego-Fabrega C et al. | β | 2024 | β |
| CLOCK gene 3'UTR and exon 9 polymorphisms show a strong association with essential hypertension in a North Indian population. | Sopori S et al. | β | 2024 | β |
| [Exploring the Causal Relationship Between Coagulation Function and Gestational Diabetes Mellitus Through Mendelian Randomization]. | Zeng F et al. | β | 2024 | β |
| Integrative analysis of multiple cell death model for precise prognosis and drug response prediction in gastric cancer. | Su W et al. | β | 2024 | β |
| No Causal Relationship Between Coagulation Factors and Sepsis-Related Risks: A Mendelian Randomization Study | Lei J et al. | β | 2024 | β |
| The effects of coagulation factors on the risk of autoimmune diseases: A Mendelian randomization study. | Li S et al. | β | 2024 | β |
| Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma. | Zhai Y et al. | β | 2023 | β |
| Identification of genomic loci regulating platelet plasminogen activator inhibitor-1 in mice. | Siebert AE et al. | β | 2023 | β |
| The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study. | Li Y et al. | β | 2023 | β |
| Characterization of Platelet Function-Related Gene Predicting Survival and Immunotherapy Efficacy in Gastric Cancer. | Xia Y et al. | β | 2022 | β |
| Circulating adipokine levels and preeclampsia: A bidirectional Mendelian randomization study. | Chen X et al. | β | 2022 | β |
| Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes. | Nieves-ColΓ³n MA et al. | β | 2022 | β |
| Cross-Ancestry Investigation of Venous Thromboembolism Genomic Predictors. | Thibord F et al. | β | 2022 | β |
| Elevated plasma levels of plasminogen activator inhibitor-1 are associated with risk of future incident venous thromboembolism. | Frischmuth T et al. | β | 2022 | β |
| Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus. | Stacey D et al. | β | 2022 | β |
| Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations. | Temprano-Sagrera G et al. | β | 2022 | β |
| SERPINE1 Overexpression Promotes Malignant Progression and Poor Prognosis of Gastric Cancer. | Chen S et al. | β | 2022 | β |
| Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis. | Guo Y et al. | β | 2021 | β |
| Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study. | Dimou NL et al. | β | 2021 | β |
| Effects of Thyroid Function on Hemostasis, Coagulation, and Fibrinolysis: A Mendelian Randomization Study. | Ellervik C et al. | β | 2021 | β |
| FGL1 as a modulator of plasma D-dimer levels: Exome-wide marker analysis of plasma tPA, PAI-1, and D-dimer. | Thibord F et al. | β | 2021 | β |
| Genetic Association of Hepatitis C-Related Mixed Cryoglobulinemia: A 10-Year Prospective Study of Asians Treated with Antivirals. | Chang ML et al. | β | 2021 | β |
| Genome-wide analyses of multiple obesity-related cytokines and hormones informs biology of cardiometabolic traits. | Meeks KAC et al. | β | 2021 | β |
| Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging. | McCartney DL et al. | β | 2021 | β |
| Immune-Related Gene SERPINE1 Is a Novel Biomarker for Diffuse Lower-Grade Gliomas <i>via</i> Large-Scale Analysis. | Huang X et al. | β | 2021 | β |
| Neuroprotective Effect of Plasminogen Activator Inhibitor-1 Antagonist in the Rat Model of Mild Traumatic Brain Injury. | Kuru BektaΕoΔlu P et al. | β | 2021 | β |
| Quantile-specific heritability of plasminogen activator inhibitor type-1 (PAI-1, aka SERPINE1) and other hemostatic factors. | Williams PT | β | 2021 | β |
| The susceptibility of SERPINE1 rs1799889 SNP in diabetic vascular complications: a meta-analysis of fifty-one case-control studies. | Chen J et al. | β | 2021 | β |
| Genetic variation, adipokines, and cardiometabolic disease. | Metz S et al. | β | 2020 | β |
| Mendelian randomisation analysis of circulating adipokines and C-reactive protein on breast cancer risk. | Robinson T et al. | β | 2020 | β |
| Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults. | Hillary RF et al. | β | 2020 | β |
| Specific inhibition of plasminogen activator inhibitor 1 reduces blood glucose level by lowering TNF-a. | Tang S et al. | β | 2020 | β |
| The role of haematological traits in risk of ischaemic stroke and its subtypes. | Harshfield EL et al. | β | 2020 | β |
| Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism. | LindstrΓΆm S et al. | β | 2019 | β |
| Haplotype analysis of SERPINE1 gene: Risk for aneurysmal subarachnoid hemorrhage and clinical outcomes. | Lin M et al. | β | 2019 | β |
| Plasminogen activator inhibitor-1 augments damage by impairing fibrinolysis after traumatic brain injury. | Griemert EV et al. | β | 2019 | β |
| Using a Targeted Proteomics Chip to Explore Pathophysiological Pathways for Incident Diabetes- The MalmΓΆ Preventive Project. | Molvin J et al. | β | 2019 | β |
| Coagulation Factors and the Risk of Ischemic Heart Disease: A Mendelian Randomization Study. | Zhao JV et al. | β | 2018 | β |
| From genome-wide association studies to Mendelian randomization: novel opportunities for understanding cardiovascular disease causality, pathogenesis, prevention, and treatment. | Benn M et al. | β | 2018 | β |
| Role of plasminogen activator inhibitor-1 in coronary pathophysiology. | Jung RG et al. | β | 2018 | β |
| What is currently known about the genetics of venous thromboembolism at the dawn of next generation sequencing technologies. | TrΓ©gouΓ«t DA et al. | β | 2018 | β |
| A null mutation in <i>SERPINE1</i> protects against biological aging in humans. | Khan SS et al. | β | 2017 | β |
| Association of Plasminogen Activator Inhibitor 1 (SERPINE1) Polymorphisms and Aneurysmal Subarachnoid Hemorrhage. | Hendrix P et al. | β | 2017 | β |
| Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease. | Song C et al. | β | 2017 | β |
| Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study. | de Vries PS et al. | β | 2017 | β |
| Genetic Effects on the Correlation Structure ofΒ CVD Risk Factors: Exome-Wide Data From a Ghanaian Population. | Kodaman N et al. | β | 2017 | β |
| Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance. | Chang ML et al. | β | 2017 | β |
| PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort. | Sherenian MG et al. | β | 2017 | β |
| Plasminogen Activator Inhibitor-1 is Regulated Through Dietary Fat Intake and Heritability: Studies in Twins. | Engstler AJ et al. | β | 2017 | β |
| Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function. | Cho SH et al. | β | 2016 | β |
| Expression of inflammation-related miRNAs in white blood cells from subjects with metabolic syndrome after 8 wk of following a Mediterranean diet-based weight loss program. | Marques-Rocha JL et al. | β | 2016 | β |
| Genetic analysis of emerging risk factors in coronary artery disease. | van Iperen EP et al. | β | 2016 | β |
| Genome-wide studies of von Willebrand factor propeptide identify loci contributing to variation in propeptide levels and von Willebrand factor clearance. | Ozel AB et al. | β | 2016 | β |
| Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies. | Yarmolinsky J et al. | β | 2016 | β |
| Association between cognition and gene polymorphisms involved in thrombosis and haemostasis. | Quinn TJ et al. | β | 2015 | β |
| Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE. | Divella R et al. | β | 2015 | β |
| Contiguous mutation syndrome in the era of high-throughput sequencing. | LangouΓ«t M et al. | β | 2015 | β |
| Dissecting the genetic determinants of hemostasis and thrombosis. | Desch KC | β | 2015 | β |
| Genetics of Plasminogen Activator Inhibitor-1 (PAI-1) in a Ghanaian Population. | White MJ et al. | β | 2015 | β |
| Genetics of Venous Thrombosis: update in 2015. | Morange PE et al. | β | 2015 | β |
| Improvement of Psychotic Symptoms and the Role of Tissue Plasminogen Activator. | Hoirisch-Clapauch S et al. | β | 2015 | β |
| The -844 G>A PAI-1 polymorphism is associated with acute coronary syndrome in Mexican population. | GarcΓa-GonzΓ‘lez IJ et al. | β | 2015 | β |
| Cautious enthusiasm about GWAS findings. | Gagnon F | β | 2014 | β |
| Clock genes in hypertension: novel insights from rodent models. | Richards J et al. | β | 2014 | β |
| Genetic variants in PLG, LPA, and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels. | Ma Q et al. | β | 2014 | β |
| Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2. | Huang J et al. | β | 2014 | β |
| Genome-wide investigation of DNA methylation marks associated with FV Leiden mutation. | AΓ―ssi D et al. | β | 2014 | β |
| Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle. | Scheer FA et al. | β | 2014 | β |
| Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. | Perry JR et al. | β | 2014 | β |
| Pleiotropic genes for metabolic syndrome and inflammation. | Kraja AT et al. | β | 2014 | β |
| Association of plasminogen activator inhibitor-type 1 (-675 4G/5G) polymorphism with pre-eclampsia: systematic review. | Morgan JA et al. | β | 2013 | β |
| Circadian regulation of renal function and potential role in hypertension. | Bonny O et al. | β | 2013 | β |
| Hemostatic factors and risk of coronary heart disease in general populations: new prospective study and updated meta-analyses. | Willeit P et al. | β | 2013 | β |
| In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time. | de Lange Z et al. | β | 2013 | β |
| PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis. | Wang S et al. | β | 2013 | β |
| SERPINE1, PAI-1 protein coding gene, methylation levels and epigenetic relationships with adiposity changes in obese subjects with metabolic syndrome features under dietary restriction. | Lopez-Legarrea P et al. | β | 2013 | β |