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Association Between Plasminogen Activator Inhibitor-1 Genetic Polymorphisms and Stroke Susceptibility

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Abstract

The plasminogen activator inhibitor-1 (PAI-1) is a candidate gene for stroke based on PAI-1’s crucial role in fibrinolytic system. However, association studies have yielded conflicting results regarding the association between PAI-1 polymorphisms and stroke susceptibility. To further elucidate the putative association, we performed a systematic review and meta-analysis to provide a complete picture of the loci investigated for association of PAI-1 polymorphism with stroke risk and to derive a precise estimation. PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched until June 2015 to identify eligible studies. Forty data sets from 39 studies with a total of 8336 cases and 14,403 controls were included. The most commonly investigated polymorphism was -675 4G/5G, followed by -844 G/A, 11053 T>G, HindIII C/G, and (CA)n. Overall, our meta-analysis provided evidence for the significant association of PAI-1 4G/5G polymorphism with an increased risk of adult but not pediatric ischemic stroke (adult: 4G/4G vs. 4G/5G + 5G/5G, OR = 1.21, 95 % CI = 1.04–1.42). In the subgroup analysis, significant association was detected in Asians (4G/4G vs. 4G/5G + 5G/5G, OR = 1.45, 95 % CI = 1.14–1.85) but not Caucasians. Moreover, we found that -844 G/A but not 11053 T>G polymorphism was associated with an increased risk of ischemic stroke (-844G/A: A/A vs. G/G: OR = 1.32, 95 % CI = 1.01–1.73). A tendency of PAI-1 4G/5G polymorphism towards a decreased risk of hemorrhagic stroke was observed (4G/4G + 4G/5G vs. 5G/5G, OR = 0.77, 95 % CI = 0.59–1.02, P = 0.066). Future well-designed studies in large well-characterized sample size and presenting results stratified by gender, age, and stroke subtype are warranted.

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References

  1. Macko RF, Kittner SJ, Epstein A, Cox DK, Wozniak MA, Wityk RJ, Stern BJ, Sloan MA et al (1999) Elevated tissue plasminogen activator antigen and stroke risk: the Stroke Prevention in Young Women Study. Stroke 30(1):7–11

    Article  CAS  PubMed  Google Scholar 

  2. Lijnen HR, Collen D (1996) Impaired fibrinolysis and the risk for coronary heart disease. Circulation 94(9):2052–2054

    Article  CAS  PubMed  Google Scholar 

  3. Vaughan DE (2003) Plasminogen activator inhibitor-1 and the calculus of mortality after myocardial infarction. Circulation 108(4):376–377. doi:10.1161/01.CIR.0000082929.85234.E7

    Article  PubMed  Google Scholar 

  4. Thogersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, Hallmans G (1998) High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation 98(21):2241–2247

    Article  CAS  PubMed  Google Scholar 

  5. Iacoviello L, Agnoli C, De Curtis A, di Castelnuovo A, Giurdanella MC, Krogh V, Mattiello A, Matullo G et al (2013) Type 1 plasminogen activator inhibitor as a common risk factor for cancer and ischaemic vascular disease: the EPICOR study. BMJ Open 3(11):e003725. doi:10.1136/bmjopen-2013-003725

    Article  PubMed  PubMed Central  Google Scholar 

  6. Klinger KW, Winqvist R, Riccio A, Andreasen PA, Sartorio R, Nielsen LS, Stuart N, Stanislovitis P et al (1987) Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc Natl Acad Sci U S A 84(23):8548–8552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Isordia-Salas I, Leanos-Miranda A, Sainz IM, Reyes-Maldonado E, Borrayo-Sanchez G (2009) Association of the plasminogen activator inhibitor-1 gene 4G/5G polymorphism with ST elevation acute myocardial infarction in young patients. Rev Esp Cardiol 62(4):365–372

    Article  PubMed  Google Scholar 

  8. Morange PE, Henry M, Tregouet D, Granel B, Aillaud MF, Alessi MC, Juhan-Vague I (2000) The A -844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers. Arterioscler, Thromb, Vasc Biol 20(5):1387–1391

    Article  CAS  Google Scholar 

  9. Tsai SJ, Hong CJ, Liou YJ, Yu YW, Chen TJ (2008) Plasminogen activator inhibitor-1 gene is associated with major depression and antidepressant treatment response. Pharmacogenet Genomics 18(10):869–875. doi:10.1097/FPC.0b013e328308bbc0

    Article  CAS  PubMed  Google Scholar 

  10. Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM (1993) The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 268(15):10739–10745

    CAS  PubMed  Google Scholar 

  11. Festa A, D’Agostino R Jr, Rich SS, Jenny NS, Tracy RP, Haffner SM (2003) Promoter (4G/5G) plasminogen activator inhibitor-1 genotype and plasminogen activator inhibitor-1 levels in blacks, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study. Circulation 107(19):2422–2427. doi:10.1161/01.CIR.0000066908.82782.3A

    Article  CAS  PubMed  Google Scholar 

  12. Eriksson P, Kallin B, Hooft FM V’t, Bavenholm P, Hamsten A (1995) Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci U S A 92(6):1851–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Grubic N, Stegnar M, Peternel P, Kaider A, Binder BR (1996) A novel G/A and the 4G/5G polymorphism within the promoter of the plasminogen activator inhibitor-1 gene in patients with deep vein thrombosis. Thromb Res 84(6):431–443

    Article  CAS  PubMed  Google Scholar 

  14. Gong LL, Peng JH, Han FF, Zhu J, Fang LH, Wang YH, Du GH, Wang HY et al (2012) Association of tissue plasminogen activator and plasminogen activator inhibitor polymorphism with myocardial infarction: a meta-analysis. Thromb Res 130(3):e43–e51. doi:10.1016/j.thromres.2012.06.015

    Article  CAS  PubMed  Google Scholar 

  15. Wiklund PG, Nilsson L, Ardnor SN, Eriksson P, Johansson L, Stegmayr B, Hamsten A, Holmberg D et al (2005) Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke 36(8):1661–1665. doi:10.1161/01.str.0000174485.10277.24

    Article  CAS  PubMed  Google Scholar 

  16. Jood K, Ladenvall P, Tjarnlund-Wolf A, Ladenvall C, Andersson M, Nilsson S, Blomstrand C, Jern C (2005) Fibrinolytic gene polymorphism and ischemic stroke. Stroke 36(10):2077–2081. doi:10.1161/01.str.0000183617.54752.69

    Article  CAS  PubMed  Google Scholar 

  17. Babu MS, Prabha TS, Kaul S, Al-Hazzani A, Shafi G, Roy S, Balakrishna N, Jyothy A et al (2012) Association of genetic variants of fibrinolytic system with stroke and stroke subtypes. Gene 495(1):76–80. doi:10.1016/j.gene.2011.12.046

    Article  CAS  PubMed  Google Scholar 

  18. Roest M, van der Schouw YT, Banga JD, Tempelman MJ, de Groot PG, Sixma JJ, Grobbee DE (2000) Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of cerebrovascular mortality in older women. Circulation 101(1):67–70

    Article  CAS  PubMed  Google Scholar 

  19. Adamski MG, Turaj W, Slowik A, Wloch-Kopec D, Wolkow P, Szczudlik A (2009) A-G-4G haplotype of PAI-1 gene polymorphisms -844 G/A, HindIII G/C, and -675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease. Acta Neurol Scand 120(2):94–100. doi:10.1111/j.1600-0404.2008.01127.x

    Article  CAS  PubMed  Google Scholar 

  20. Ranellou K, Paraskeva A, Kyriazopoulos P, Batistatou A, Evangelou A, El-Aly M, Zis P, Tavernarakis A et al (2015) Polymorphisms in prothrombotic genes in young stroke patients in Greece: a case-controlled study. Blood Coagul Fibrinolysis 26(4):430–435. doi:10.1097/mbc.0000000000000274

    Article  CAS  PubMed  Google Scholar 

  21. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  22. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    CAS  PubMed  Google Scholar 

  23. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. doi:10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  24. Akar N, Akar E, Yilmaz E, Deda G (2001) Plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish children with cerebral infarct and effect on factor V 1691 A mutation. J Child Neurol 16(4):294–295

    Article  CAS  PubMed  Google Scholar 

  25. Assawamakin A, Sriratanaviriyakul N, Lalerd Y, Thongnoppakhun W, Praditsap O, Tongsima S, Pithukpakorn M (2012) Meta-analysis of the plasminogen activator inhibitor-1 (PAI-1) gene with insertion/deletion 4G/5G polymorphism and its susceptibility to ischemic stroke in Thai population. Asian Biomedicine 6(2):203–217

    CAS  Google Scholar 

  26. Balcerzyk A, Zak I, Emich-Widera E, Kopyta I, Iwanicki T, Pilarska E, Pienczk-Reclawowicz K, Kacinski M et al (2011) The plasminogen activator inhibitor-1 gene polymorphism in determining the risk of pediatric ischemic stroke—case control and family-based study. Neuropediatrics 42(2):67–70. doi:10.1055/s-0031-1279785

    Article  CAS  PubMed  Google Scholar 

  27. Bang CO, Park HK, Ahn MY, Shin HK, Hwang KY, Hong SY (2001) 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and insertion/deletion polymorphism of the tissue-type plasminogen activator gene in atherothrombotic stroke. Cerebrovasc Dis 11(4):294–299, 47656

    Article  CAS  PubMed  Google Scholar 

  28. Catto AJ, Carter AM, Stickland M, Bamford JM, Davies JA, Grant PJ (1997) Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism and levels in subjects with cerebrovascular disease. Thromb Haemost 77(4):730–734

    CAS  PubMed  Google Scholar 

  29. Chen CH, Eng HL, Chang CJ, Tsai TT, Lai ML, Chen HY, Liu CJ, Lin TM (2003) 4G/5G promoter polymorphism of plasminogen activator inhibitor-1, lipid profiles, and ischemic stroke. J Lab Clin Med 142(2):100–105. doi:10.1016/s0022-2143(03)00063-5

    Article  CAS  PubMed  Google Scholar 

  30. Crainich P, Jenny NS, Tang Z, Arnold AM, Kuller LH, Manolio T, Sharrett AR, Tracy RP (2003) Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly. J Thromb Haemost 1(8):1799–1804

    Article  CAS  PubMed  Google Scholar 

  31. Elbaz A, Cambien F, Amarenco P (2001) Plasminogen activator inhibitor genotype and brain infarction. Circulation 103(2):e13–e14, author reply e13-14

    Article  CAS  PubMed  Google Scholar 

  32. Esparza-Garcia JC, Santiago-German D, Guadalupe Valades-Mejia M, Hernandez-Juarez J, Aguilar-Sosa E, Leanos-Miranda A, Alvarado-Moreno A, Majluf-Cruz A, Isordia-Salas I (2015) GLU298ASP and 4G/5G polymorphisms and the risk of ischemic stroke in young individuals. Can J Neurol Sci:1–7. doi:10.1017/cjn.2015.45

  33. Geng D, Zhu J, Chen G, Tang X, Yang Q, Li J, Liu F (2008) Association of plasminogen activator inhibitor-1 4G/5G promoter polymorphism with recurrent cerebral infarction in China’s North Jiangsu Province. Neural Regeneration Research 3(7):791–794

    CAS  Google Scholar 

  34. Guan LX, Wang JX, Wang RL, Du XY, Zhang AJ, Song BH, Li HB (2004) Effect of gene polymorphism of PAI-1 gene promotor region on patients with essential hypertension complicated by cerebral infarction. Zhonghua Lao Nian Yi Xue Za Zhi 23(11):4–7

    Google Scholar 

  35. Guo X, Shi XM, Zhao XY, Zhou XM, Xing HY, Song GY (2011) The relationship between PAI-1 promoter region 4G/5G gene polymorphism, ACE I/D gene polymorphism and cerebral stroke. Ji Chu Yi Xue Yu Lin Chuang 31(11):1238–1241

    Google Scholar 

  36. Hindorff LA, Schwartz SM, Siscovick DS, Psaty BM, Longstreth WT Jr, Reiner AP (2002) The association of PAI-1 promoter 4G/5G insertion/deletion polymorphism with myocardial infarction and stroke in young women. J Cardiovasc Risk 9(2):131–137

    Article  PubMed  Google Scholar 

  37. Huang X, Li Y, Huang Z, Wang C, Xu Z (2014) Pai-1 gene variants and COC use are associated with stroke risk: a case-control study in the Han Chinese women. J Mol Neurosci 54(4):803–810. doi:10.1007/s12031-014-0418-0

    Article  CAS  PubMed  Google Scholar 

  38. Jeppesen LL, Wilhelmsen K, Nielsen LB, Jorgensen HS, Nakayama H, Raaschou HO, Nielsen JD, Olsen TS et al (1998) An insertion/deletion polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene is associated with plasma levels but not with stroke risk in the elderly. J Stroke Cerebrovasc Dis 7(6):385–390

    Article  CAS  PubMed  Google Scholar 

  39. Kain K, Young J, Bamford J, Bavington J, Grant PJ, Catto AJ (2002) Determinants of plasminogen activator inhibitor-1 in South Asians with ischaemic stroke. Cerebrovasc Dis 14(2):77–83

    Article  CAS  PubMed  Google Scholar 

  40. Katakami N, Takahara M, Kaneto H, Shimizu I, Ohno K, Ishibashi F, Osonoi T, Kashiwagi A et al (2010) Accumulation of gene polymorphisms related to plaque disruption and thrombosis is associated with cerebral infarction in subjects with type 2 diabetes. Diabetes Care 33(2):390–395. doi:10.2337/dc09-1518

    Article  CAS  PubMed  Google Scholar 

  41. Komitopoulou A, Platokouki H, Kapsimali Z, Pergantou H, Adamtziki E, Aronis S (2006) Mutations and polymorphisms in genes affecting hemostasis proteins and homocysteine metabolism in children with arterial ischemic stroke. Cerebrovasc Dis 22(1):13–20. doi:10.1159/000092332

    Article  CAS  PubMed  Google Scholar 

  42. Liang L, He HH, Cai JY, Lin B (2014) The association of 4G/5G and -844 G/A polymorphisms in the promoter region of plasminogen activator inhibitor-1 and their haplotype with ischemic stroke. Zhong Guo Shi Yong Yi Yao 9(23):99–101

    Google Scholar 

  43. Liu S, Yang L, Wang X (1998) The study of the plasma PAI-1 activity and its promotor region gene polymorphism in acute cerebral infarction. Chin J Neurol 31(5):264–266

    Google Scholar 

  44. Liu Z, Zhao B (2008) The association of beta fibrinogen -148 C/T gene and plasminogen activator inhibitor-1 -675 4G/5G gene polymorphisms with cerebral infarction. Shen Jing Ji Bing Yu Jing Shen Wei Sheng 8(2):94–97

    Google Scholar 

  45. Ma LY, Zhao Y, WX Y, Liu YX, Liu LS, Lindpaintner K (2000) Association between genetic polymorphisms of type I plasminogen activator inhibitor and ischemic stroke. Gao Xue Ya Za Zhi 8(4):315–317

    Google Scholar 

  46. Maguire J, Thakkinstian A, Levi C, Lincz L, Bisset L, Sturm J, Scott R, Whyte S et al (2011) Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 polymorphisms on 90-day ischemic stroke functional outcome: a novel finding. J Stroke Cerebrovasc Dis 20(2):134–144. doi:10.1016/j.jstrokecerebrovasdis.2009.10.011

    Article  PubMed  Google Scholar 

  47. Nowak-Gottl U, Strater R, Kosch A, von Eckardstein A, Schobess R, Luigs P, Nabel P, Vielhaber H et al (2001) The plasminogen activator inhibitor (PAI)-1 promoter 4G/4G genotype is not associated with ischemic stroke in a population of German children. Childhood Stroke Study Group. Eur J Haematol 66(1):57–62

    Article  CAS  PubMed  Google Scholar 

  48. Petrovic D, Milanez T, Kobal J, Bregar D, Potisk KP, Peterlin B (2003) Prothrombotic gene polymorphisms and atherothrombotic cerebral infarction. Acta Neurol Scand 108(2):109–113

    Article  CAS  PubMed  Google Scholar 

  49. Saidi S, Slamia LB, Mahjoub T, Ammou SB, Almawi WY (2007) Association of PAI-1 4G/5G and -844G/A gene polymorphism and changes in PAI-1/tPA levels in stroke: a case-control study. J Stroke Cerebrovasc Dis 16(4):153–159. doi:10.1016/j.jstrokecerebrovasdis.2007.02.002

    Article  PubMed  Google Scholar 

  50. Tang XB, Liu SX, Geng DQ, Zhou J (2008) Association between 4G/5G genetic polymorphisms in the promotor region of the plasminogen activator inhibitor-1 and stroke. Shen Jing Ji Bing Yu Jing Shen Wei Sheng 8(1):33–37

    Google Scholar 

  51. Tang YL, Huang Q, Qin PY (2009) Correlation between plasminogen activator inhibitor-1 4G/5G polymorphisms and cerebral hemorrhage. Zhong Feng Yu Shen Jing Ji Bing Za Zhi 04:392–395

    Google Scholar 

  52. Xu B, Zhang CY, Xian BX (2006) The activity of plasma plasminogen activator inhibitor-1 and 4G/5G polymorphism in its promoter region in acute cerebral infarction. Zhongguo Yi Shi Jin Xiu Za Zhi 29(15):26–28

    CAS  Google Scholar 

  53. Yeh PS, Lin HJ, Li YH, Lin KC, Cheng TJ, Chang CY, Ke DS (2004) Prognosis of young ischemic stroke in Taiwan: impact of prothrombotic genetic polymorphisms. Thromb Haemost 92(3):583–589. doi:10.1267/thro04090000

    CAS  PubMed  Google Scholar 

  54. Yi GH (2004) A study of the plasma plasminogen activator inhibitor-1 activity and its promoter region gene polymorphism in acute cerebral infarction. Qing Dao Da Xue Yi Xue Yuan Xue Bao 40(3):229–231

    CAS  Google Scholar 

  55. Zee RY, Cook NR, Cheng S, Reynolds R, Erlich HA, Lindpaintner K, Ridker PM (2004) Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Hum Mol Genet 13(4):389–396. doi:10.1093/hmg/ddh039

    Article  CAS  PubMed  Google Scholar 

  56. Zhang C, Li J, Li L, Luo B (2001) The study of PAI-1 promotor region gene polymorphism in cerebrovascular disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 18(5):383–387

    CAS  PubMed  Google Scholar 

  57. Zhang YD, Sun Q, Liu Y, Shi JP, Di Q (2001) The association of PAI-1 gene polymorphism with cerebral infarction and recurrent cerebral infarction. Lin Chuang Shen Jing Bing Xue Za Zhi 14(5):262–265

    Google Scholar 

  58. Natesirinilkul R, Sasanakul W, Chuansumrit A, Kadegasem P, Visudtibhan A, Wongwerawattanakoon P, Sirachainan N (2014) Global fibrinolytic activity, PAI-1 level, and 4G/5G polymorphism in Thai children with arterial ischemic stroke. J Stroke Cerebrovasc Dis 23(10):2566–2572. doi:10.1016/j.jstrokecerebrovasdis.2014.05.025

    Article  PubMed  Google Scholar 

  59. Ladenvall C, Csajbok L, Nylen K, Jood K, Nellgard B, Jern C (2009) Association between factor XIII single nucleotide polymorphisms and aneurysmal subarachnoid hemorrhage. J Neurosurg 110(3):475–481. doi:10.3171/2008.7.jns08272

    Article  CAS  PubMed  Google Scholar 

  60. Reiner AP, Schwartz SM, Frank MB, Longstreth WT Jr, Hindorff LA, Teramura G, Rosendaal FR, Gaur LK et al (2001) Polymorphisms of coagulation factor XIII subunit A and risk of nonfatal hemorrhagic stroke in young white women. Stroke 32(11):2580–2586

    Article  CAS  PubMed  Google Scholar 

  61. Di Carlo A (2009) Human and economic burden of stroke. Age Ageing 38(1):4–5. doi:10.1093/ageing/afn282

    Article  PubMed  Google Scholar 

  62. O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, Rangarajan S, Islam S et al (2010) Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet 376(9735):112–123. doi:10.1016/S0140-6736(10)60834-3

    Article  PubMed  Google Scholar 

  63. Bevan S, Traylor M, Adib-Samii P, Malik R, Paul NL, Jackson C, Farrall M, Rothwell PM et al (2012) Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke 43(12):3161–3167. doi:10.1161/STROKEAHA.112.665760

    Article  CAS  PubMed  Google Scholar 

  64. Bak S, Gaist D, Sindrup SH, Skytthe A, Christensen K (2002) Genetic liability in stroke: a long-term follow-up study of Danish twins. Stroke 33(3):769–774

    Article  PubMed  Google Scholar 

  65. Seshadri S, Beiser A, Pikula A, Himali JJ, Kelly-Hayes M, Debette S, DeStefano AL, Romero JR et al (2010) Parental occurrence of stroke and risk of stroke in their children: the Framingham study. Circulation 121(11):1304–1312. doi:10.1161/CIRCULATIONAHA.109.854240

    Article  PubMed  PubMed Central  Google Scholar 

  66. Casas JP, Hingorani AD, Bautista LE, Sharma P (2004) Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol 61(11):1652–1661. doi:10.1001/archneur.61.11.1652

    Article  PubMed  Google Scholar 

  67. Markus HS (2012) Stroke genetics: prospects for personalized medicine. BMC Med 10:113. doi:10.1186/1741-7015-10-113

    Article  PubMed  PubMed Central  Google Scholar 

  68. Endler G, Lalouschek W, Exner M, Mitterbauer G, Haring D, Mannhalter C (2000) The 4G/4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients with minor stroke than in controls. Br J Haematol 110(2):469–471

    Article  CAS  PubMed  Google Scholar 

  69. Deng S, Zhu G, Liu F, Zhang H, Qin X, Li L, Zhiyi H (2010) CYP4F2 gene V433M polymorphism is associated with ischemic stroke in the male Northern Chinese Han population. Prog Neuropsychopharmacol Biol Psychiatry 34(4):664–668. doi:10.1016/j.pnpbp.2010.03.009

    Article  CAS  PubMed  Google Scholar 

  70. Slowik A, Dziedzic T, Turaj W, Pera J, Glodzik-Sobanska L, Szermer P, Malecki MT, Figlewicz DA et al (2004) A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males. Stroke 35(7):1589–1593. doi:10.1161/01.STR.0000132194.24663.3d

    Article  CAS  PubMed  Google Scholar 

  71. Nowak-Gottl U, Gunther G, Kurnik K, Strater R, Kirkham F (2003) Arterial ischemic stroke in neonates, infants, and children: an overview of underlying conditions, imaging methods, and treatment modalities. Semin Thromb Hemost 29(4):405–414. doi:10.1055/s-2003-42590

    Article  PubMed  Google Scholar 

  72. Bernard TJ, Goldenberg NA, Armstrong-Wells J, Amlie-Lefond C, Fullerton HJ (2008) Treatment of childhood arterial ischemic stroke. Ann Neurol 63(6):679–696. doi:10.1002/ana.21406

    Article  PubMed  Google Scholar 

  73. Garcia-Gonzalez IJ, Valle Y, Sandoval-Pinto E, Valdes-Alvarado E, Valdez-Haro A, Munoz-Valle JF, Flores-Salinas HE, Figuera-Villanueva LE et al (2015) The -844 G>A PAI-1 polymorphism is associated with acute coronary syndrome in Mexican population. Dis Markers 2015:460974. doi:10.1155/2015/460974

    PubMed  PubMed Central  Google Scholar 

  74. Lin S, Huiya Z, Bo L, Wei W, Yongmei G (2009) The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome. Endocrine 36(3):503–509. doi:10.1007/s12020-009-9255-2

    Article  CAS  PubMed  Google Scholar 

  75. Henry M, Tregouet DA, Alessi MC, Aillaud MF, Visvikis S, Siest G, Tiret L, Juhan-Vague I (1998) Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations: a family study with part of the Stanislas Cohort. Arterioscler, Thromb, Vasc Biol 18(1):84–91

    Article  CAS  Google Scholar 

  76. Morange PE, Saut N, Alessi MC, Yudkin JS, Margaglione M, Di Minno G, Hamsten A, Humphries SE et al (2007) Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI-1, and metabolic parameters: the HIFMECH study. Arterioscler, Thromb, Vasc Biol 27(10):2250–2257. doi:10.1161/ATVBAHA.107.149468

    Article  CAS  Google Scholar 

  77. Ghosh AK, Vaughan DE (2012) PAI-1 in tissue fibrosis. J Cell Physiol 227(2):493–507. doi:10.1002/jcp.22783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Attia J, Thakkinstian A, Wang Y, Lincz L, Parsons M, Sturm J, McGettigan P, Scott R et al (2007) The PAI-1 4G/5G gene polymorphism and ischemic stroke: an association study and meta-analysis. J Stroke Cerebrovasc Dis 16(4):173–179. doi:10.1016/j.jstrokecerebrovasdis.2007.03.002

    Article  PubMed  Google Scholar 

  79. Tsantes AE, Nikolopoulos GK, Bagos PG, Tsiara CG, Kapsimali V, Travlou A, Vaiopoulos G (2007) Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke: a meta-analysis. Blood Coagul Fibrinolysis 18(5):497–504. doi:10.1097/MBC.0b013e3281ec4eee

    Article  CAS  PubMed  Google Scholar 

  80. Cao Y, Chen W, Qian Y, Zeng Y, Liu W (2014) Plasminogen activator inhibitor-1 4G/5G polymorphism and ischemic stroke risk: a meta-analysis in Chinese population. Int J Neurosci 124(12):874–881. doi:10.3109/00207454.2014.886577

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The study is supported by the National Key Technology R&D Program for the 12th Five-Year Plan of People’s Republic of China (No. 2011BAI08B05) and the Science and Technology Support Program of the Department of Science and Technology of Sichuan Province (2014FZ0066).

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    Authors and Affiliations

    1. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China

      Xin Hu, Xin Zan, Zhiyi Xie, Sen Lin, Hao Li & Chao You

    2. West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, China

      Yunke Li

    Authors
    1. Xin Hu
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    2. Xin Zan
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    3. Zhiyi Xie
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    4. Yunke Li
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    5. Sen Lin
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    6. Hao Li
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    7. Chao You
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    Corresponding author

    Correspondence to Chao You.

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    The authors declare that they have no competing interests.

    Additional information

    Xin Hu, Xin Zan and Zhiyi Xie contributed equally to this work.

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    Hu, X., Zan, X., Xie, Z. et al. Association Between Plasminogen Activator Inhibitor-1 Genetic Polymorphisms and Stroke Susceptibility. Mol Neurobiol 54, 328–341 (2017). https://doi.org/10.1007/s12035-015-9549-8

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    • DOI: https://doi.org/10.1007/s12035-015-9549-8

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