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血清脑源性神经营养因子(BDNF)升高而非BDNF基因Val66Met多态性与自闭症谱系障碍相关。

Elevated Serum Brain-Derived Neurotrophic Factor (BDNF) but not BDNF Gene Val66Met Polymorphism Is Associated with Autism Spectrum Disorders.

作者信息

Meng Wei-Dong, Sun Shao-Jun, Yang Jie, Chu Rui-Xue, Tu Wenjun, Liu Qiang

机构信息

Department of Laboratory Medicine, Liaocheng People's Hospital, No. 67, Dongchang West Road, Liaocheng, 252000, China.

Department of Pharmacy, Liaocheng Herbalist Hospital, Liaocheng, China.

出版信息

Mol Neurobiol. 2017 Mar;54(2):1167-1172. doi: 10.1007/s12035-016-9721-9. Epub 2016 Jan 28.

DOI:10.1007/s12035-016-9721-9
PMID:26820673
Abstract

The aim of our study was to illuminate the potential role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder (ASD). We measured the circulating levels of BDNF in serum and BDNF gene (Val66Met) polymorphisms, in which two indicators were then compared between ASD and normal controls. A total of 82 drug-naïve ASD children and 82 age- and gender-matched normal controls were enrolled in the study. Their serum BDNF levels were detected by the ELISA. BDNF Val66Met polymorphism genotyping was conducted as according to the laboratory's standard protocol in laboratory. The ASD severity assessment was mainly determined by the score of the Childhood Autism Rating Scale (CARS). ELISA assay showed that the mean serum BDNF level of children with ASD was significantly (P < 0.0001) higher than that of the control cases (17.75 ± 5.43 vs. 11.49 ± 2.85 ng/ml; t = 9.236). Besides, the serum BDNF levels and CARS scores (P < 0.0001) were positively related. And, the BDNF genotyping results showed that there was no difference between the ASD cases and the control. Among the children with ASD, the mean serum BDNF level of Met/Met group was lower than other groups. According to the ROC curve generated from our clinical data, the optimal cutoff value of serum BDNF levels, an indicator for diagnosis of ASD, was projected to be 12.50 ng/ml. Thus, it yielded a corresponding sensitivity of 81.7 % and the specificity of 66.9 %. Accordingly, area value under the curve was 0.836 (95 % CI, 0.774-0.897); the positive predictive value (PPV) and the negative predictive value (NPV) were 70.1 and 79.1 %, respectively. These results suggested that rather than Val66Met polymorphism, BDNF was more possible to impact the pathogenesis of ASD.

摘要

我们研究的目的是阐明脑源性神经营养因子(BDNF)在自闭症谱系障碍(ASD)中的潜在作用。我们测量了血清中BDNF的循环水平以及BDNF基因(Val66Met)多态性,然后在ASD患者与正常对照之间对这两项指标进行比较。本研究共纳入82例未接受过药物治疗的ASD儿童以及82例年龄和性别匹配的正常对照。采用酶联免疫吸附测定法(ELISA)检测他们血清中的BDNF水平。BDNF Val66Met多态性基因分型按照实验室的标准方案在实验室中进行。ASD严重程度评估主要通过儿童自闭症评定量表(CARS)得分来确定。ELISA检测显示,ASD儿童的血清BDNF平均水平显著高于对照组(P < 0.0001)(17.75 ± 5.43 vs. 11.49 ± 2.85 ng/ml;t = 9.236)。此外,血清BDNF水平与CARS得分呈正相关(P < 0.0001)。并且,BDNF基因分型结果显示ASD病例与对照组之间无差异。在ASD儿童中,Met/Met组的血清BDNF平均水平低于其他组。根据我们临床数据生成的ROC曲线,血清BDNF水平作为ASD诊断指标的最佳截断值预计为12.50 ng/ml。因此,其相应的灵敏度为81.7%,特异性为66.9%。相应地,曲线下面积值为0.836(95% CI,0.774 - 0.897);阳性预测值(PPV)和阴性预测值(NPV)分别为70.1%和79.1%。这些结果表明,相比于Val66Met多态性,BDNF更有可能影响ASD的发病机制。

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