Department of Community Medicine and School of Public Health, University of Hong Kong, Hong Kong.
J Neurol Neurosurg Psychiatry. 2013 Mar;84(3):322-8. doi: 10.1136/jnnp-2012-303791. Epub 2012 Dec 12.
Polymorphisms of the gene encoding the serotonin transporter-specifically, length variation in the serotonin--transporter-linked polymorphic region (5-HTTLPR), a single-nucleotide polymorphism in the 5-HTTLPR (rs25531), and variable number of tandem repeats (VNTR) in the second intron 2 (STin2)--have been implicated in the development of post-stroke depression (PSD).
To evaluate the association between polymorphisms of the serotonin transporter gene and PSD in the medical literature.
Random-effects meta-analyses were conducted on cross-sectional, case-control and cohort studies examining relations between polymorphisms of the gene encoding the serotonin transporter and the risk of developing PSD.
Four studies comprising 260 stroke patients with PSD and 381 without were included. Our analyses showed a significant and positive association between the homozygous short variation (S) allele genotype of the 5-HTTLPR (SS) and PSD (random-effects pooled OR 2.05, 95% CI 1.41 to 2.98, z=3.79, p<0.001). Our analyses also showed a significant and negative association between the homozygous long variation (L) allele genotype of the 5-HTTLPR (LL) and PSD (random-effects OR 0.52, 95% CI 0.27 to 0.97, z=-2.07, p=0.039). No statistically significant association of PSD with heterozygous S and L allele genotype for 5-HTTLPR or other polymorphisms with rs25531 and STin2 VNTR was found. Heterogeneity and publication bias were not statistically significant. The major limitation of this meta-analysis is that we could not assess the interaction between stroke, environmental stress and PSD.
The 5-HTTLPR SS genotype may be a risk factor for PSD. The 5-HTTLPR LL genotype showed a significant negative association with PSD. Further research to assess the sensitivity and specificity of predicting the risk of developing PSD by screening for the 5-HTTLPR genotype in stroke patients is required.
编码血清素转运体的基因多态性——特别是血清素转运体连接多态区（5-HTTLPR）的长度变化、5-HTTLPR 中的单核苷酸多态性（rs25531）以及第二内含子 2 中的可变串联重复（VNTR）（STin2）——与中风后抑郁（PSD）的发展有关。
在医学文献中评估血清素转运体基因多态性与 PSD 之间的关系。
对横断面、病例对照和队列研究进行了随机效应荟萃分析，以研究编码血清素转运体的基因多态性与 PSD 发生风险之间的关系。
纳入了四项研究，共纳入了 260 例 PSD 中风患者和 381 例非 PSD 中风患者。我们的分析表明，5-HTTLPR 的纯合短变异（S）等位基因基因型（SS）与 PSD 之间存在显著正相关（随机效应汇总 OR 2.05，95%CI 1.41 至 2.98，z=3.79，p<0.001）。我们的分析还表明，5-HTTLPR 的纯合长变异（L）等位基因基因型（LL）与 PSD 之间存在显著负相关（随机效应 OR 0.52，95%CI 0.27 至 0.97，z=-2.07，p=0.039）。未发现 5-HTTLPR 的杂合 S 和 L 等位基因基因型或其他与 rs25531 和 STin2 VNTR 的多态性与 PSD 相关的统计学显著相关性。异质性和发表偏倚无统计学意义。本荟萃分析的主要局限性是我们无法评估中风、环境应激和 PSD 之间的相互作用。
5-HTTLPR SS 基因型可能是 PSD 的一个危险因素。5-HTTLPR LL 基因型与 PSD 呈显著负相关。需要进一步研究通过筛选中风患者的 5-HTTLPR 基因型来评估预测 PSD 发生风险的敏感性和特异性。
