IRCCS Fondazione Don Carlo Gnocchi ONLUS, 50143 Florence, Italy.
Int J Mol Sci. 2020 Nov 10;21(22):8438. doi: 10.3390/ijms21228438.
Brain-Derived Neurotrophic Factor (BDNF) and its rs6265 single nucleotide polymorphism (SNP) play an important role in post-stroke recovery. We investigated the correlation between rs6265 SNP and recovery outcome, measured by the modified Barthel index, in 49 patients with stroke hospitalized in our rehabilitation center at baseline (T0) and after 30 sessions of rehabilitation treatment (T1); moreover, we analyzed the methylation level of the CpG site created or abolished into rs6265 SNP. In total, 11 patients (22.4%) were heterozygous GA, and 32 (65.3%) and 6 (12.2%) patients were homozygous GG and AA, respectively. The univariate analysis showed a significant relationship between the rs6265 SNP and the modified Barthel index cut-off (χ(1, N = 48) = 3.86, = 0.049), considering patients divided for carrying (A+) or not carrying (A-) the A allele. A higher percentage of A- patients obtained a favorable outcome, as showed by the logistic regression model corrected by age and time since the stroke onset, compared with the A+ patients (OR: 5.59). At baseline (T0), the percentage of methylation was significantly different between GG (44.6 ± 1.1%), GA (39.5 ± 2.8%) and AA (28.5 ± 1.7%) alleles ( < 0.001). After rehabilitation (T1), only patients A- showed a significant increase in methylation percentages (mean change = 1.3, CI: 0.4-2.2, = 0.007). This preliminary study deserves more investigation to confirm if rs6265 SNP and its methylation could be used as a biological marker of recovery in patients with stroke undergoing rehabilitation treatment.
脑源性神经营养因子（BDNF）及其 rs6265 单核苷酸多态性（SNP）在卒中后恢复中起着重要作用。我们研究了 rs6265 SNP 与基线（T0）和 30 次康复治疗后（T1）在我们康复中心住院的 49 例卒中患者的改良巴氏指数（modified Barthel index）恢复结果之间的相关性；此外，我们还分析了 rs6265 SNP 产生或消除的 CpG 位点的甲基化水平。总共有 11 例（22.4%）患者为杂合 GA，32 例（65.3%）和 6 例（12.2%）患者为纯合 GG 和 AA。单因素分析显示，rs6265 SNP 与改良巴氏指数截断值之间存在显著关系（χ(1, N = 48) = 3.86，= 0.049），考虑到携带（A+）或不携带（A-）A 等位基因的患者。与 A+患者相比，A-患者获得良好结局的比例更高，这是由年龄和卒中发病时间校正的 logistic 回归模型显示的（OR：5.59）。在基线（T0）时，GG（44.6 ± 1.1%）、GA（39.5 ± 2.8%）和 AA（28.5 ± 1.7%）等位基因的甲基化百分比差异具有显著性（<0.001）。康复后（T1），仅 A-患者的甲基化百分比显示出显著增加（平均变化= 1.3，CI：0.4-2.2，= 0.007）。这项初步研究需要进一步调查，以确认 rs6265 SNP 及其甲基化是否可作为接受康复治疗的卒中患者恢复的生物标志物。
