Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation-Reference-Cited by-同舟云学术

Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation

Published:2012-12-06 Issue:24 Volume:120 Page:4873-4881
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Huang Jie¹,Sabater-Lleal Maria²,Asselbergs Folkert W.³⁴⁵,Tregouet David⁶,Shin So-Youn⁷,Ding Jingzhong⁸,Baumert Jens⁹,Oudot-Mellakh Tiphaine⁶,Folkersen Lasse²,Johnson Andrew D.¹¹⁰,Smith Nicholas L.¹¹¹²¹³,Williams Scott M.¹⁴,Ikram Mohammad A.¹⁵¹⁶,Kleber Marcus E.¹⁷¹⁸,Becker Diane M.¹⁹,Truong Vinh²⁰,Mychaleckyj Josyf C.²¹,Tang Weihong²²,Yang Qiong¹²³,Sennblad Bengt²,Moore Jason H.²⁴,Williams Frances M. K.²⁵,Dehghan Abbas¹⁵²⁶,Silbernagel Günther²⁷,Schrijvers Elisabeth M. C.¹⁵²⁶,Smith Shelly²⁸,Karakas Mahir²⁹,Tofler Geoffrey H.³⁰,Silveira Angela²,Navis Gerjan J.³¹,Lohman Kurt³²,Chen Ming-Huei²³,Peters Annette⁹,Goel Anuj³³³⁴,Hopewell Jemma C.³⁵,Chambers John C.³⁶³⁷,Saleheen Danish³⁸³⁹,Lundmark Per⁴⁰,Psaty Bruce M.⁴¹¹²,Strawbridge Rona J.²,Boehm Bernhard O.⁴²,Carter Angela M.⁴³,Meisinger Christa⁹,Peden John F.³³³⁴,Bis Joshua C.⁴⁴,McKnight Barbara⁴⁵,Öhrvik John²,Taylor Kent⁴⁶,Franzosi Maria Grazia⁴⁷,Seedorf Udo⁴⁸,Collins Rory³⁵,Franco-Cereceda Anders⁴⁹,Syvänen Ann-Christine⁴⁰,Goodall Alison H.⁵⁰,Yanek Lisa R.¹⁹,Cushman Mary⁵¹⁵²,Müller-Nurasyid Martina⁵³⁵⁴⁵⁵,Folsom Aaron R.²²,Basu Saonli⁵⁶,Matijevic Nena⁵⁷,van Gilst Wiek H.⁵⁸,Kooner Jaspal S.³⁷,Hofman Albert¹⁵²⁶,Danesh John³⁹,Clarke Robert⁵⁹,Meigs James B.⁶⁰⁶¹,Kathiresan Sekar⁶²⁶³⁶⁴,Reilly Muredach P.⁶⁵,Klopp Norman⁶⁶,Harris Tamara B.⁶⁷,Winkelmann Bernhard R.⁶⁸,Grant Peter J.⁴³,Hillege Hans L.⁵⁸,Watkins Hugh³³³⁴,Spector Timothy D.²⁵,Becker Lewis C.⁶⁹,Tracy Russell P.⁷⁰,März Winfried¹⁸⁷¹⁷²,Uitterlinden Andre G.¹⁶²⁶,Eriksson Per²,Cambien Francois²⁰,Morange Pierre-Emmanuel⁷³,Koenig Wolfgang²⁹,Soranzo Nicole⁷²⁵,van der Harst Pim⁵⁸,Liu Yongmei²⁸⁷⁴,O'Donnell Christopher J.¹¹⁰⁷⁵,Hamsten Anders², , , ,

Affiliation:

1. National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study, Framingham, MA;

2. Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;

3. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands;

4. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands;

5. Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands;

6. Inserm Unite Mixte de Recherche (UMR)_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;

7. Wellcome Trust Sanger Institute, Hinxton, United Kingdom;

8. Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC;

9. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;

10. Division of Intramural Research, NHLBI, Bethesda, MD;

11. Department of Epidemiology, University of Washington, Seattle, WA;

12. Group Health Research Institute, Group Health Cooperative, Seattle, WA;

13. Seattle Epidemiologic Research and Information Center, VA Office of Research and Development, Seattle, WA;

14. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN; Rotterdam Study:

15. Department of Epidemiology, Erasmus Medical Center (MC) Medical Center, Rotterdam, The Netherlands;

16. Department of Internal Medicine, Erasmus MC Medical Center, Rotterdam, The Netherlands;

17. Ludwigshafen Risk and Cardiovascular Health (LURIC) Study Nonprofit LLC, Freiburg, Germany;

18. Mannheim Institute of Public Health, Medical Faculty, University of Heidelberg, Mannheim, Germany;

19. Division of Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD;

20. Inserm UMR_S 937, ICAN Institute, Université Pierre et Marie Curie (UPMC, Paris 06), Paris, France;

21. Center for Public Health Genomics, University of Virginia, Charlottesville, VA;

22. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;

23. Department of Biostatistics, Boston University, Boston, MA;

24. Department of Genetics and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH;

25. Department of Twin Research & Genetic Epidemiology, King's College London, London, United Kingdom;

26. Netherlands Consortium for Healthy Aging, Leiden, The Netherlands;

27. Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, Department of Internal Medicine, Eberhard-Karls-University Tübingen, Tübingen, Germany;

28. Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;

29. Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany;

30. Royal North Shore Hospital, University of Sydney, Sydney, Australia;

31. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;

32. Department of Biostatistical Sciences, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC;

33. Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;

34. Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;

35. Clinical Trial Service Unit, University of Oxford, United Kingdom;

36. Epidemiology and Biostatistics, Imperial College, London, London, United Kingdom;

37. Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, United Kingdom;

38. Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan;

39. Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom;

40. Molecular Medicine and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden;

41. Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA;

42. Division of Endocrinology, Diabetes and Metabolism, Graduate School of Molecular Diabetology and Endocrinology, University of Ulm, Ulm, Germany;

43. Division of Cardiovascular and Diabetes Research, Leeds University, Leeds, United Kingdom;

44. Department of Medicine, University of Washington, Seattle, WA;

45. Department of Biostatistics, University of Washington, Seattle, WA;

46. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA;

47. Department of Cardiovascular Research, Istituto Mario Negri, Milano, Italy;

48. Gesellschaft für Arterioskleroseforschunge V, Leibniz-Institut für Arterioskleroseforschung an der Universität Münster (LIFA), Münster, Germany;

49. Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;

50. Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom;

51. Departments of Medicine and Pathology, University of Vermont, Burlington, VT; GeneSTAR:

52. Departments of Medicine and Pathology, University of Vermont, Burlington, VT;

53. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;

54. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology and Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany;

55. Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany;

56. Division of Biostatistics, University of Minnesota, Minneapolis, MN;

57. Hemostasis Laboratory, University of Texas Health Science Center at Houston, Houston, TX; Cardiovascular Health Study:

58. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;

59. Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom;

60. General Medicine Division, Massachusetts General Hospital, Boston, MA;

61. Department of Medicine at Harvard Medical School, Boston, MA;

62. Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA;

63. Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA;

64. Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA;

65. Cardiovascular Institute, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;

66. Division of Molecular Epidemiology, Helmholtz Zentrum München, German Resrarch Center for Environmental Health, Neuherberg, Germany;

67. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD;

68. Cardiology Team Sachsenhausen, Frankfurt am Main, Germany;

69. Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD;

70. Department of Pathology and Biochemistry, University of Vermont College of Medicine, Burlington, VT;

71. Synlab Academy, Mannheim, Germany;

72. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz Austria;

73. Inserm UMR_S 626, Université de la Méditerranée, Marseille, France;

74. Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC; and

75. Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Abstract

Abstract 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 × 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 × 10−10); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 × 10−8); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 × 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/120/24/4873/1361003/zh805012004873.pdf

Reference37 articles.

1. Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease.;Aznar;Br Heart J,1988

2. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction.;Hamsten;Lancet,1987

3. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction.;Hamsten;N Engl J Med,1985

4. Plasminogen-activator inhibitor type 1 and coronary artery disease.;Kohler;N Engl J Med,2000

5. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries.;Lupu;Arterioscler Thromb,1993

Cited by 85 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. No Causal Relationship Between Coagulation Factors and Sepsis-Related Risks: A Mendelian Randomization Study;2024-08-06

2. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment;Journal of Thrombosis and Haemostasis;2023-12

3. Characterization of the Prognosis and Tumor Microenvironment of Cellular Senescence-related Genes through scRNA-Seq and Bulk RNA-Seq Analysis in GC;Recent Patents on Anti-Cancer Drug Discovery;2023-10-03

4. Identification of genomic loci regulating platelet plasminogen activator inhibitor-1 in mice;Journal of Thrombosis and Haemostasis;2023-10

5. The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study;BMC Medicine;2023-05-25