纤溶酶原激活物抑制剂-1活性及其基因多态性与新疆维吾尔族静脉血栓栓塞症的相关性

古丽尼格尔·吾布力; 艾力曼·马合木提; 古丽米热·吐尼牙孜; 夏玉宁; 胡雪梅; 张韵娇

doi:10.13201/j.issn.1001-1439.2014.07.007

纤溶酶原激活物抑制剂-1活性及其基因多态性与新疆维吾尔族静脉血栓栓塞症的相关性

- 新疆医科大学第一附属医院心脏中心心力衰竭科(乌鲁木齐, 830011)
基金项目:
新疆重大疾病医学重点实验室-省部共建国家重点实验室培育基地项目 (No:SKLIB-XJMDR-2012-7)

详细信息

通讯作者: 艾力曼·马合木提,E-mail:nayisha2006@hotmail.com

中图分类号: R541.6

收稿日期: 2014-04-10

Association between PAI-1 activity and its polymorphism in Uygur patients with venous thromboembolism of Xinjiang

- Heart Center, First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China

More Information

Corresponding author: Ailiman MAHEMUTI, E-mail: nayisha2006@hotmail.com

Received Date: 10 April 2014

摘要

摘要: 目的:探讨纤溶酶原激活物抑制剂 (PAI) -1活性及启动子区4G/5G基因多态性在静脉血栓栓塞症 (VTE) 发病机制中的作用。方法:收集我院2008-01-2011-06住院的VTE患者198例, 其中维族86例, 汉族112例;健康对照组212例, 其中维族92例, 汉族120例。采用PCR-PFLP技术检测PAI-1基因启动子区域的4G/5G多态性。结果:①PAI-1基因4G/5G的3种基因型在维族VTE组和对照组的分布频率分别为:4G/4G型 (81.39%:66.30%)、4G/5G型 (15.12%:21.74%) 和5G/5G型 (3.49%:12.04%);汉族VTE组和对照组基因分布频率分别为:4G/4G型 (67.86%:51.67%)、4G/5G型 (19.64%:29.17%) 和5G/5G型 (12.50%:19.17%), 其基因型分布频率在同民族病例与对照组基因型分布比较, 差异有统计学意义 (P＜0.05)。②维汉两民族VTE组和对照组中, PAI-1基因4G/5G各基因型之间血浆PAI-1活性差异有统计学意义 (P＜0.05), 其中4G/4G为基因型的血浆PAI-1活性高于同组同民族4G/5G、5G/5G型者。③通过非条件logistic回归模型校正后, PAI-1基因4G/4G基因型 (OR=1.914, 95%CI 3.345⁵.708, P=0.001) 及血浆PAI-1活性 (OR=2.167, 95%CI1.489³.153, P=0.000) 是维族VTE患者的独立危险因素, 而吸烟 (OR=2.867, 95%CI 1.062⁶.586, P=0.010) 和血浆PAI-1活性 (OR=1.357, 95%CI1.141¹.614, P=0.001) 是汉族VTE患者的的独立危险因素。结论:VTE患者血浆PAI-1活性均偏高, 血浆PAI-1活性为维、汉两民族VTE患者的独立危险因素。维、汉两民族VTE组PAI-1基因4G/4G基因型频率较正常人群高, 4G/4G基因型是维吾尔族VTE患者的独立危险因素。
- 纤溶酶原激活物抑制剂-1 /
- 基因多态性 /
- 静脉血栓栓塞症 /
- 维吾尔族
Abstract: Objective: To investigate the association between single nucleotide insertion/deletion (4G/5G) polymorphism of PAI-1gene and venous thromboembolism (VTE).Method: The 198 cases including 86 Uygur and 112 Han ethnic diagnosed with VTE by the First Affiliated Hospital of Xinjiang Medical University between January 2008 to June 2011 were admitted in this study.And 212 population including 92 Uygur ethnic and Han 120 ethnic were studied as controls.PCR-RFLP was applied to detect the polymorphism of PAI-1gene 4G/5G polymorphism in the promoter region.Result: The PAI-1gene 4G/5G polymorphism distribution in Uygur VTE patients and control groups were:4G/4G (81.4% vs. 66.3%), 4G/5G (15.1% vs. 21.7%) and 5G/5G (3.5% vs. 12%), respectively;and in Han VTE patients and control groups were:4G/4G (67.9% vs. 51.7%), 4G/5G (19.6% vs. 29.2%) and 5G/5G (12.5% vs. 19.2%), respectively, and there were significant differences in distribution of PAI-1 4G/5G polymorphism between VTE patients and controls (P＜0.05).Besides, plasma PAI-1activity in PAI-1gene 4G/4G genotype were statistically higher than 4G/5G and 5G/5G genotype (P＜0.05).Multifactor logistic regression analysis showed that, PAI-1gene 4G/4G genotype (OR=1.914, 95%CI 3.345~.708, P=0.001) and plasma PAI-1activity (OR=2.167, 95%CI 1.489~3.153, P=0.000) were independent risk factors for Uygur patients while smoking (OR=2.867, 95%CI 1.062~6.586, P=0.024) and plasma PAI-1activity (OR=1.357, 95%CI 1.141~1.614, P=0.001) were independent risk factors for Han VTE patients.Conclusion: The plasma PAI-1activity was higher in VTE patients compared to normal population in both Uygur and Han ethnic group, and plasma PAI-1activity was an independent risk factor for VTE patients in Uygur and Han ethnics.The frequency of PAI-1gene 4G/4G genotype was higher in VTE population than normal population, and 4G/4G genotype is an independent risk factor for Uygur VTE patients.
- plasminogen activator inhibitor-1 /
- gene polymorphism /
- venous thromboembolism /
- Uyghur

HTML全文

参考文献(34)

[1]	BEZEMER I D, BARE L A, DOGGEN C J, et al.Gene variants associated with deep vein thrombosis[J].JAMA, 2008, 299:1306-1314.
[2]	YE S, GREEN F R, SCARABIN P Y, et al.The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1activity but not with risk of myocardial infarction in the ECTIM study.Etude Cas Temoins de I'nfarctus du Mycocarde[J].Thromb Haemost, 1995, 74:837-841.
[3]	STEGNAR M, UHRIN P, PETERNEL P, et al.The 4G/5G sequence polymorphism in the promoter of plasminogen activator inhibitor-1 (PAI-1) gene:relationship to plasma PAI-1level in venous thromboembolism[J].Thromb Haemost, 1998, 79:975-979.
[4]	KUPELI E, VERDI H, SIMSEK A, et al.Genetic mutations in Turkish population with pulmonary embolism and deep venous thrombosis[J].Clin Appl Thromb Hemost, 2011, 17:87-94.
[5]	AKHTER M S, BISWAS A, RANJAN R, et al.Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism is seen in higher frequency in the Indian patients with deep vein thrombosis[J].Clin Appl Thromb Hemost, 2010, 16:184-188.
[6]	SHAMMAA D M, SABBAGH A S, TAHER A T, et al.Plasminogen Activator Inhibitor-1 (PAI-1) gene 4G/5G alleles frequency distribution in the Lebanese population[J].Mol Biol Rep, 2008, 35:453-457.
[7]	凯丽比努尔.阿布都热合曼, 艾力曼.马合木提, 夏玉宁, 等.维族亚甲基四氢叶酸还原酶基因多态性及血浆同型半胱氨酸水平与静脉血栓栓塞症的相关性研究[J].中华心血管病杂志, 2012, 12:1030-1036.
[8]	艾力曼.马合木提, 西艾木西卡买尔.艾合买提.516例维、汉两民族住院肺血栓栓塞症患者危险因素构成特点分析[J].中国循证医学杂志, 2012, 23 (5):520-524.
[9]	YANG S L, HE B X, LIU H L, et al.Apolipoprotein E gene polymorphisms and risk for coronary artery disease in Chinese Xinjiang Uygur and Han population[J].Chin Med Sci J, 2004, 19:150-154.
[10]	LIU F, MA Y T, YANG Y N, et al.Current status of primary hypertension in Xinjiang:an epidemiological study of Han, Uygur and Hazakh populations[J].Zhonghua Yi Xue Za Zhi, 2010, 90:3259-3263.
[11]	YAO J, MA Y, XIE X, et al.Association of rs1805127 polymorphism of KCNE1 gene with atrial fibrillation in Uigur population of Xinjiang[J].Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2011, 28:436-440.
[12]	PRANDONI P, BILORA F, MARCHIORI A, et al.An association between atherosclerosis and venous thrombosis[J].N Engl J Med, 2003, 348:1435-1441.
[13]	PRANDONI P.Venous thromboembolism and atherosclerosis:is there a link?[J].J Thromb Haemost, 2007, 5 (Suppl 1):270-275.
[14]	LOWE G D.Common risk factors for both arterial and venous thrombosis[J].Br J Haematol, 2008, 140:488-495.
[15]	TORBICKI A, PERRIER A, KONSTANTINIDES S, et al.Guidelines on the diagnosis and management of acute pulmonary embolism:the Task Force for the Diagnosis and Management of Acute pulmonary Embolism of the European Society of Cardiology (ESC)[J].Eur Heart J, 2008, 29:2276-2315.
[16]	中国成人血脂异常防治指南制订联合委员会.中国成人血脂异常防治指南[J].中华心血管病杂志, 2007, 35 (5):390-419.
[17]	中国高血压防治指南修订委员会.中国高血压防治指南2010[J].中华心血管病杂志, 2011, 39 (7):579-614.
[18]	HENRY M, TREGOUET D A, ALESSI M C, et al.Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1activity and antigen plasma concentrations:a family study with part of the Stanislas Cohort[J].Arterioscler Thromb Vasc Biol, 1998, 18:84-91.
[19]	FRANCIS C W.Plasminogen activator inhibitor-1levels and polymorphisms[J].Arch Pathol Lab Med, 2002, 126:1401-1404.
[20]	ZLLER B, GARCíA DE FRUTOS P, DAHLBäCK B.A common 4G allele in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene as a risk factor forpulmonary embolism and arterial thrombosis in hereditary protein S deficiency[J].Thromb Haemost, 1998, 79:802-807.
[21]	SARTORI M T, WIMAN B, VETTORE S, et al. 4G/5G polymorphism of PAI-1gene promoter and fibrinolytic capacity in patients with deep vein thrombosis[J].Thromb Haemost, 1998, 80:956-960.
[22]	RIDKER P M, HENNEKENS C H, LINDPAINTNER K, et al.Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohort of US men[J].Circulation, 1997, 95:59
[23]	AKAR N, YILMAZ E, AKAR E, et al.Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish deep vein thrombotic patients with and without FV1691 G-A[J].Thromb Res, 2000, 97:227-230.
[24]	翟振国, 王辰, 杨媛华, 等.纤溶酶原激活物抑制剂-1启动子区域基因多态性与肺血栓栓塞症的相关性研究[J].中华医学杂志, 2006, 86 (10):1313-1317.
[25]	ERIKSSON P, KALLIN B, VAN'T HOOFT F M, et al.Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1gene is associated with myocardial infarction[J].Proc Natl Acad Sci USA, 1995, 92:1851-1855.
[26]	YAMADA N, WADA H, NAKASE T, et al.Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis[J].Blood Coagul Fibrinolysis, 1995, 6:627-633.
[27]	马涵英, 赵铁夫, 雒芳芳, 等.肺动脉血栓栓塞与组织型纤溶酶原激活剂及纤溶酶原激活物抑制剂的关系[J].中华老年心脑血管病杂志, 2010, 12 (11):967-969.
[28]	ERICKSON L A, FICI G J, LUND J E, et al.Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1gene[J].Nature, 1990, 346:74-76.
[29]	GALIOTO N J, DANLEY D L, VAN MAANEN R J, et al.Recurrent venous thromboembolism[J].Am Fam Physician, 2011, 83:293-300.
[30]	KOBAYASHI T, NAKAMURA M, SAKUMA M, et al.Incidence of pulmonary thromboembolism (PTE) and new guidelines for PTE prophylaxis in Japan[J].Clin Hemorheol Microcirc, 2006, 35:257-259.
[31]	TSAI A W, CUSHMAN M, ROSAMOND W D, et al.Cardiovascular risk factors and venous thromboembolism incidence:the Longitudinal Investigation of Thromboembolism Etiology[J].Arch Intern Med, 2002, 162:1182-1189.
[32]	VAN DER HAGEN P B, FOLSOM A R, JENNY N S, et al.Subclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study[J].J Thromb Haemost, 2006, 4:1903-1908.
[33]	REICH L M, FOLSOM A R, KEY N S, et al.Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism[J].J Thromb Haemost, 2006, 4:1909-1913.
[34]	BECATTINI C, AGNELLI G, PRANDONI P, et al.A prospective study on cardiovascular events after acute pulmonary embolism[J].Eur Heart J, 2005, 26:77-83.