Associations of BDNF genotype and promoter methylation with acute and long-term stroke outcomes in an East Asian cohort.
Associations of BDNF genotype and promoter methylation with acute and long-term stroke outcomes in an East Asian cohort.
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DOI：
10.1371/journal.pone.0051280
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yoon JS
中科院分区：
文献类型：
--
作者：
Kim JM;Stewart R;Park MS;Kang HJ;Kim SW;Shin IS;Kim HR;Shin MG;Cho KH;Yoon JS
脑源性神经营养因子（BDNF）在脑卒中后的恢复中起着重要作用。BDNF的分泌受遗传和表观遗传的影响。本研究旨在探讨BDNF val66met多态性和启动子甲基化状态是否与卒中后2周和1年的预后相关。共有286例患者在入院时和卒中后两周进行了评估，222例（78%）在一年后进行了随访，以评估卒中在急性和慢性阶段的后果。根据改良的兰金量表将卒中结局分为良好和不良。测量卒中严重程度（国立卫生研究院卒中量表）、身体残疾（Barthel指数）和认知功能（简易精神状态检查）。采用logistic回归、重复测量方差分析和偏相关检验研究BDNF基因型和甲基化状态与卒中结局和评估量表评分的关系。BDNF val66met多态性与2周和1年时的不良结局独立相关，并与此期间身体残疾和认知功能恶化相关。较高的BDNF启动子甲基化状态与1年时的不良结局以及身体残疾和认知功能的恶化独立相关。BDNF在脑卒中后恢复中的作用得到了支持，并建议将BDNF的遗传和表观遗传特征作为预后生物标志物和药物开发的靶点进行临床应用。
Brain derived neurotrophic factor (BDNF) has been shown to play an important role in poststroke recovery. BDNF secretion is influenced by genetic and epigenetic profiles. This study aimed to investigate whether BDNF val66met polymorphism and promoter methylation status were associated with outcomes at two weeks and one year after stroke. A total of 286 patients were evaluated at the time of admission and two weeks after stroke, and 222 (78%) were followed one year later in order to evaluate consequences of stroke at both acute and chronic stages. Stroke outcomes were dichotomised into good and poor by the modified Rankin Scale. Stroke severity (National Institutes of Health Stroke Scale), physical disability (Barthel Index), and cognitive function (Mini-Mental State Examination) were measured. Associations of BDNF genotype and methylation status on stroke outcomes and assessment scale scores were investigated using logistic regression, repeated measures ANOVA and partial correlation tests. BDNF val66met polymorphism was independently associated with poor outcome at 2 weeks and at 1 year, and with worsening physical disability and cognitive function over that period. Higher BDNF promoter methylation status was independently associated with worse outcomes at 1 year, and with the worsening of physical disability and cognitive function. No significant genotype-methylation interactions were found. A role for BDNF in poststroke recovery was supported, and clinical utility of BDNF genetic and epigenetic profile as prognostic biomarkers and a target for drug development was suggested.
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DOI：
10.1523/jneurosci.1786-08.2008
发表时间：
2008-10-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lubin FD;Roth TL;Sweatt JD
通讯作者：
Sweatt JD
影响因子：
10.6
作者：
Kunugi, H;Iijima, Y;Yoshikawa, T
通讯作者：
Yoshikawa, T
影响因子：
3.7
作者：
Béjot Y;Mossiat C;Giroud M;Prigent-Tessier A;Marie C
通讯作者：
Marie C
影响因子：
56.9
作者：
Martinowich, K;Hattori, D;Sun, YE
通讯作者：
Sun, YE
影响因子：
4.8
作者：
FOLSTEIN, MF;FOLSTEIN, SE;MCHUGH, PR
通讯作者：
MCHUGH, PR