Neurology, 12222University of California, Irvine, CA, USA.
Dept. Neurology, University of California, Los Angeles; and California Rehabilitation Institute, Los Angeles, CA, USA.
Neurorehabil Neural Repair. 2022 Feb;36(2):131-139. doi: 10.1177/15459683211062899. Epub 2021 Dec 21.
Patients show substantial differences in response to rehabilitation therapy after stroke. We hypothesized that specific genetic profiles might explain some of this variance and, secondarily, that genetic factors are related to cerebral atrophy post-stroke.
The phase 3 ICARE study examined response to motor rehabilitation therapies. In 216 ICARE enrollees, DNA was analyzed for presence of the BDNF valmet and the ApoE ε4 polymorphism. The relationship of polymorphism status to 12-month change in motor status (Wolf Motor Function Test, WMFT) was examined. Neuroimaging data were also evaluated (n=127).
Subjects were 61±13 years old (mean±SD) and enrolled 43±22 days post-stroke; 19.7% were BDNF valmet carriers and 29.8% ApoE ε4 carriers. Carrier status for each polymorphism was not associated with WMFT, either at baseline or over 12 months of follow-up. Neuroimaging, acquired 5±11 days post-stroke, showed that BDNF valmet polymorphism carriers had a 1.34-greater degree of cerebral atrophy compared to non-carriers (P=.01). Post hoc analysis found that age of stroke onset was 4.6 years younger in subjects with the ApoE ε4 polymorphism (P=.02).
Neither the valmet BDNF nor ApoE ε4 polymorphism explained inter-subject differences in response to rehabilitation therapy. The BDNF valmet polymorphism was associated with cerebral atrophy at baseline, echoing findings in healthy subjects, and suggesting an endophenotype. The ApoE ε4 polymorphism was associated with younger age at stroke onset, echoing findings in Alzheimer's disease and suggesting a common biology. Genetic associations provide insights useful to understanding the biology of outcomes after stroke.
患者在中风后的康复治疗反应存在很大差异。我们假设，特定的基因谱可能解释了部分差异，其次，遗传因素与中风后的大脑萎缩有关。
3 期 ICARE 研究检查了对运动康复治疗的反应。在 216 名 ICARE 参与者中，分析了 DNA 中 BDNF valmet 和 ApoE ε4 多态性的存在情况。还检查了多态性状态与 12 个月运动状态变化（Wolf 运动功能测试，WMFT）的关系。还评估了神经影像学数据（n=127）。
受试者年龄为 61±13 岁（平均值±标准差），中风后入组时间为 43±22 天；19.7%为 BDNF valmet 携带者，29.8%为 ApoE ε4 携带者。两种多态性在基线或 12 个月的随访中均与 WMFT 无关。中风后 5±11 天获得的神经影像学检查显示，BDNF valmet 多态性携带者的大脑萎缩程度比非携带者大 1.34 倍（P=.01）。事后分析发现，具有 ApoE ε4 多态性的受试者的中风发病年龄年轻了 4.6 岁（P=.02）。
BDNF valmet 或 ApoE ε4 多态性都不能解释对康复治疗反应的个体差异。BDNF valmet 多态性与基线时的大脑萎缩有关，这与健康受试者的研究结果一致，提示存在一个表型。ApoE ε4 多态性与中风发病年龄较小有关，这与阿尔茨海默病的研究结果一致，提示存在共同的生物学机制。遗传相关性为理解中风后结局的生物学机制提供了有用的见解。
