大脑静脉血栓症中的XI和ABO因子之间的基因-基因相互作用:BEAST研究
Gie Ken-Dror1, Ida Martinelli1, Elvira Grandone1
1From the Institute of Cardiovascular Research Royal Holloway (G.K.-D., P.S.), University of London (ICR2UL), United Kingdom; Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico (I.M., S.M.P., M.A., P.B., E.P.), A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; Moncucco Hospital Group (I.M., E.G.), Lugano, Switzerland; Atherosclerosis and Thrombosis Unit (E.G., G.F., D.C.), I.R.C.C.S. Fondazione "Casa Sollievo della Sofferenza", S. Giovanni Rotondo; Medical and Surgical Department (E.G.), University of Foggia, Italy; Department of Obstetrics (E.G.), Gynaecology and Perinatal Medicine, First Sechenov University, Moscow, Russia; Neurology (S.H., J.P., E.H., T.T.), Helsinki University Hospital and University of Helsinki, Finland; Department of Clinical Neuroscience (E.L., K.J., T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (E.L., K.J., T.T.), Sahlgrenska University Hospital, Gothenburg, Sweden; Medical Genetics (M. Margaglione, R.S.), Department of Clinical and Experimental Medicine, University of Foggia, Italy; Normandy University (V.L.C.D.), UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit and INSERM CIC-CRB 1404; Department of Neurology (A.B.T.), Rouen University Hospital, France; Neurology Unit (M.Z.), Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS of Reggio Emilia; Department of Clinical and Experimental Medicine (M. Mancuso), Neurological Institute, University of Pisa, Italy; UMC Utrecht Brain Center (Y.M.R.), Department of Neurology and Neurosurgery, University Medical Center Utrecht, the Netherlands; Department of Neurology (B.B.W.), University of Virginia, Charlottesville, VA; Department of Neurology (J.J.M., A.T.), University of Utah, Salt Lake City; Department of Neurology (S.Z., M.C.B., J.M.C.), Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, the Netherlands; Department of Neurosciences (R.L.), Experimental Neurology, KU Leuven-University of Leuven; VIB Center for Brain & Disease Research; Department of Neurology, University Hospitals Leuven, Belgium; Department of Pathophysiology and Transplantation (E.P.), Università degli Studi di Milano, Milan; Department of Clinical and Experimental Sciences (P. Costa), Neurology Clinic; Division of Biology and Genetics (M.C.), Department of Molecular and Translational Medicine, University of Brescia, Italy; Stroke Center (D.A.D.S.), Centro Hospitalar Universitário Lisboa Central; CEEM and Institute of Anatomy (D.A.D.S.), Faculdade de Medicina; Instituto de Medicina Molecular João Lobo Antunes (D.A.D.S., J.M.F.), Universidade de Lisboa; Department of Neurosciences (S.G.R., P. Canhao), Hospital of Santa Maria, University of Lisbon, Portugal; Stroke Clinic (A.A.), National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City; Department of Neurology (K.S.), University of Athens School of Medicine, Eginition Hospital, Athens, Greece; McMaster University (A.H., R.D., G.P.), Pathology and Molecular Medicine, Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Medicine and Surgery (A.P.), University of Parma, Stroke Care Program, Department of Emergency, Parma University Hospital, Italy; Stroke Division (V.N.T.), Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia; and Department of Clinical Neuroscience (P.S.), Imperial College Healthcare NHS Trust, London, United Kingdom.
基因XI (F11) 和ABO因子之间的基因相互作用显著增加脑静脉血栓形成 (CVT) 的风险. 具有特定F11和ABO基因型的个体面临患CVT的4至14倍的风险.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 血栓形成研究研究
- 疾病病因学 疾病病因学
背景情况:
- 在多因素性疾病中,基因与基因的相互作用至关重要.
- 在诸如脑静脉血栓症 (CVT) 这样的疾病中缺失遗传性可能源于基因相互作用.
- 这项研究侧重于CVT中的XI因子 (F11) 和ABO基因相互作用.
研究的目的:
- 调查因子XI (F11) 和ABO基因与脑静脉血栓症 (CVT) 相关的相互作用.
- 在CVT患者中量化F11和ABO基因型组合相关的风险.
主要方法:
- 利用生物存储库的数据来确定阴静脉血栓形成病因学 (BEAST) 国际合作.
- 招募了欧洲血统的CVT患者.
- 采用共主导模型来评估F11和ABO基因和CVT状态之间的相互作用.
主要成果:
- 研究了882名CVT患者和1205名对照人群.
- 对于F11和ABO位点的风险等位基异构的个体,CVT风险增加了3.9倍.
- 在两个位点对风险等位基具有同位素的个体表现出13.9倍的CVT风险增加.
- 与特定的F11基因型相结合的非O血型进一步增加了CVT风险.
结论:
- 因子XI (F11) 和ABO基因之间的相互作用大大增加了脑静脉血栓症 (CVT) 的风险.
- F11和ABO基因变异的综合作用将CVT风险提高4至14倍.
- 这些基因-基因相互作用有助于理解CVT的遗传基础.
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