Traylor Matthew, Rutten-Jacobs Loes C A, Thijs Vincent, Holliday Elizabeth G, Levi Chris, Bevan Steve, Malik Rainer, Boncoraglio Giorgio, Sudlow Cathie, Rothwell Peter M, Dichgans Martin, Markus Hugh S
From the Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (M.T., L.C.A.R.-J., H.S.M.); Department of Medical and Molecular Genetics, King's College London, London, United Kingdom (M.T.); Laboratory of Neurobiology, Vesalius Research Center, VIB, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium (V.T.); Department of Neurology, Austin Health and Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia (V.T.); School of Medicine and Public Health (E.G.H.) and Centre for Clinical Epidemiology and Biostatistics, Hunter Medical Research Institute and School of Medicine and Public Health (C.L.), University of Newcastle, Newcastle, NSW, Australia; Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia (E.G.H.); School of Life Science, University of Lincoln, Lincoln, United Kingdom (S.B.); Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany (R.M., M.D.); Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.B.); Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (C.S.); Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom (P.M.R.); and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.).
Stroke. 2016 May;47(5):1174-9. doi: 10.1161/STROKEAHA.115.011625. Epub 2016 Apr 12.
White matter hyperintensities (WMH) are increased in patients with lacunar stroke. Whether this is because of shared pathogenesis remains unknown. Using genetic data, we evaluated whether WMH-associated genetic susceptibility factors confer risk of lacunar stroke, and therefore whether they share pathogenesis.
We used a genetic risk score approach to test whether single nucleotide polymorphisms associated with WMH in community populations were associated with magnetic resonance imaging-confirmed lacunar stroke (n=1,373), as well as cardioembolic (n=1,331) and large vessel (n=1,472) Trial of Org 10172 in Acute Stroke Treatment subtypes, against 9,053 controls. Second, we separated lacunar strokes into those with WMH (n=568) and those without (n=787) and tested for association with the risk score in these 2 groups. In addition, we evaluated whether WMH-associated single nucleotide polymorphisms are associated with lacunar stroke, or in the 2 groups.
The WMH genetic risk score was associated with lacunar stroke (odds ratio [OR; 95% confidence interval [CI]]=1.14 [1.06-1.22]; P=0.0003), in patients both with and without WMH (WMH: OR [95% CI]=1.15 [1.05-1.26]; P=0.003 and no WMH: OR [95% CI]=1.11 [1.02-1.21]; P=0.019). Conversely, the risk score was not associated with cardioembolic stroke (OR [95% CI]=1.03 [0.97-1.09]; P=0.63) or large vessel stroke (OR [95% CI]=0.99 [0.93,1.04]; P=0.39). However, none of the WMH-associated single nucleotide polymorphisms passed Bonferroni-corrected significance for association with lacunar stroke.
Genetic variants that influence WMH are associated with an increased risk of lacunar stroke but not cardioembolic or large vessel stroke. Some genetic susceptibility factors seem to be shared across different radiological manifestations of small vessel disease.
腔隙性卒中患者的白质高信号（WMH）增多。这是否由于共同的发病机制尚不清楚。利用基因数据，我们评估了与WMH相关的遗传易感性因素是否会增加腔隙性卒中的风险，以及它们是否具有共同的发病机制。
我们采用遗传风险评分方法，以检验社区人群中与WMH相关的单核苷酸多态性是否与磁共振成像确诊的腔隙性卒中（n = 1373）、心源性栓塞性卒中（n = 1331）和大动脉粥样硬化性卒中（n = 1472）（急性卒中治疗中组织纤溶酶原激活剂10172试验亚型）相关，对照组为9053人。其次，我们将腔隙性卒中分为伴有WMH的（n = 568）和不伴有WMH的（n = 787），并在这两组中检验与风险评分的相关性。此外，我们评估了与WMH相关的单核苷酸多态性是否与腔隙性卒中相关，或在这两组中是否相关。
WMH遗传风险评分与腔隙性卒中相关（优势比[OR；95%置信区间[CI]] = 1.14 [1.06 - 1.22]；P = 0.0003），在伴有和不伴有WMH的患者中均如此（伴有WMH：OR [95% CI] = 1.15 [1.05 - 1.26]；P = 0.003；不伴有WMH：OR [95% CI] = 1.11 [1.02 - 1.21]；P = 0.019）。相反，风险评分与心源性栓塞性卒中（OR [95% CI] = 1.03 [0.97 - 1.09]；P = 0.63）或大动脉粥样硬化性卒中（OR [95% CI] = 0.99 [0.93, 1.04]；P = 0.39）无关。然而，没有一个与WMH相关的单核苷酸多态性在与腔隙性卒中的关联中通过Bonferroni校正的显著性检验。
影响WMH的基因变异与腔隙性卒中风险增加相关，但与心源性栓塞性或大动脉粥样硬化性卒中无关。一些遗传易感性因素似乎在小血管疾病的不同影像学表现中是共同的。
