Zhao Qiang, Guo Yi, Yang Dong, Yang Tiansong, Meng Xianghui
Department of Neurosurgery, Chinese PLA General Hospital & PLA Medical School, Beijing, 100853, China.
Department of Neurosurgery, Baoding No. 1 Hospital, Baoding, 071000, China.
Mol Neurobiol. 2016 Apr;53(3):1699-1705. doi: 10.1007/s12035-015-9120-7. Epub 2015 Feb 21.
Polymorphisms in the 5-HTT and BDNF genes are shown to affect their function at the molecular and serum level. Prior work has tried to correlate the polymorphisms with post-stroke depression (PSD), the results nevertheless remain indefinitive. A plausible reason accounting for the uncertainty relates to the small sample of each published trial. In this study, we have performed a comprehensive meta-analysis in order to evaluate the effects of 5-HTT and BDNF polymorphisms (5-HTTLPR, STin2 VNTR, 5-HTR2a 102 T/C, Val66Met) on genetic risk of PSD. Human case-control trials were identified by computer-assisted and manual searches. The article search was performed until October 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effects meta-analysis to measure the effects 5-HTT and BDNF polymorphisms exerted on PSD. We also performed test of heterogeneity, test of publication bias, and sensitivity analysis to examine the reliability and stability of combined effects. 5-HTTLPR was clearly associated with genetic risk of PSD. The association seemed to be more pronounced in the homozygous model (OR = 0.34, 95% CI = 0.23-0.51, P(Q-test) = 0.63). Both the heterozygous model and the recessive model showed 50% decreased risk of PSD (OR = 0.50, 95% CI = 0.37-0.67, P(Q-test) = 0.91; OR = 0.50, 95% CI = 0.36-0.70, P(Q-test) = 0.43, respectively). Such significant association was also detected for Caucasian and Asian. These results were reliable and stable based on related analyses. Taken together, 5-HTTLPR polymorphism of the 5-HTT gene seems to protect against the occurrence of PSD. Small sample size for the polymorphisms within 5-HTT and BDNF genes may have caused underestimated associations, and a larger study is required to further assess the relations.
5-羟色胺转运体(5-HTT)基因和脑源性神经营养因子(BDNF)基因的多态性在分子水平和血清水平上均显示会影响其功能。先前的研究试图将这些多态性与中风后抑郁症(PSD)联系起来,但其结果仍不明确。导致这种不确定性的一个合理原因与每项已发表试验的样本量较小有关。在本研究中,我们进行了一项全面的荟萃分析,以评估5-HTT和BDNF基因多态性(5-HTTLPR、STin2可变数目串联重复序列、5-羟色胺受体2a 102 T/C、缬氨酸66蛋氨酸)对PSD遗传风险的影响。通过计算机辅助搜索和人工搜索确定人类病例对照试验。文献检索截至2014年10月。采用固定效应荟萃分析计算比值比(OR)和95%置信区间(CI),以衡量5-HTT和BDNF基因多态性对PSD的影响。我们还进行了异质性检验、发表偏倚检验和敏感性分析,以检验合并效应的可靠性和稳定性。5-HTTLPR与PSD的遗传风险明显相关。在纯合子模型中,这种关联似乎更为显著(OR = 0.34,95% CI = 0.23 - 0.51,P(Q检验)= 0.63)。杂合子模型和隐性模型均显示PSD风险降低了50%(OR分别为0.50,95% CI = 0.37 - 0.67,P(Q检验)= 0.91;OR = 0.50,95% CI = 0.36 - 0.70,P(Q检验)= 0.43)。在白种人和亚洲人群中也检测到了这种显著关联。基于相关分析,这些结果是可靠且稳定的。综上所述,5-HTT基因的5-HTTLPR多态性似乎可预防PSD的发生。5-HTT和BDNF基因内多态性的样本量较小可能导致关联被低估,需要进行更大规模的研究来进一步评估它们之间的关系。