Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder
Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder
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DOI：
10.1038/mp.2008.116
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发表时间：
2010-05-01
影响因子：
11
通讯作者：
Serretti, A.
中科院分区：
文献类型：
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作者：
Kato, M.;Serretti, A.
这篇系统综述总结了抗抑郁药反应和副作用的药物遗传学研究。在我们回顾的17个基因中，8个基因进入荟萃分析（SLC 6A 4，HTR 1A，HTR 2A，TPH 1，编码β-3亚基的基因，脑源性神经营养因子（BDNF），HTR 3A和HTR 3B）。TPH 1 218 C/C基因型（7项研究，754例受试者）与更好的反应显著相关（比值比，OR = 1.62; P = 0.005），种族间无异质性。在BDNF 66 Val/Met多态性内的Met变体受试者中也观察到更好的反应（4项研究，490例受试者; OR = 1.63，P = 0.02）。内含子2内可变数目串联重复序列多态性（STin 2）12/12基因型在亚洲人中显示出更好的反应趋势（STin 2：5项研究，686例受试者; OR = 3.89，P = 0.03）。至于副作用，5-羟色胺转运体基因启动子多态性（5-HTTLPR）I（9项研究，2642例受试者）和HTR 2A-1438 G/G（7项研究，801例受试者）的合并OR分别与显著的风险调节（OR = 0.64，P = 0.0005）和（OR = 1.91，P = 0.0006）相关。有趣的是，当仅用选择性5-羟色胺再摄取抑制剂诱导的副作用进行分析时，这种显著性变得更加稳健（5-HTTLPR：P = 0.0001，HTR 2A：P < 0.0001）。其他变体未观察到显著结果。这些结果未针对每个变体、表型和亚类的多次检测进行校正。这将需要P < 0.0023的Bonferroni显著性水平。虽然在研究中存在一些异质性，但我们的发现表明5-HTTLPR，STin 2，HTR 1A，HTR 2A，TPH 1和BDNF可能调节抗抑郁反应。Molecular Psychiatry（2010）15，473-500; doi：10.1038/mp.2008.116; 2008年11月4日在线发表
This systematic review summarizes pharmacogenetic studies on antidepressant response and side effects. Out of the 17 genes we reviewed, 8 genes were entered into the meta-analysis (SLC6A4, HTR1A, HTR2A, TPH1, gene encoding the beta-3 subunit, brain-derived neurotrophic factor (BDNF), HTR3A and HTR3B). TPH1 218C/C genotype (7 studies, 754 subjects) was significantly associated with a better response (odds ratio, OR = 1.62; P = 0.005) with no heterogeneity between ethnicities. A better response was also observed in subjects with the Met variant within the BDNF 66Val/Met polymorphism (4 studies, 490 subjects; OR = 1.63, P = 0.02). Variable number of tandem repeats polymorphism within intron 2 (STin2) 12/12 genotype showed a trend toward a better response in Asians (STin2: 5 studies, 686 subjects; OR = 3.89, P = 0.03). As for side effects, pooled ORs of serotonin transporter gene promoter polymorphism (5-HTTLPR) I (9 studies, 2642 subjects) and HTR2A - 1438G/G (7 studies, 801 subjects) were associated with a significant risk modulation (OR = 0.64, P = 0.0005) and (OR = 1.91, P = 0.0006), respectively. Interestingly, this significance became more robust when analyzed with side effect induced by selective serotonin reuptake inhibitors only (5-HTTLPR: P = 0.0001, HTR2A: P < 0.0001). No significant result could be observed for the other variants. These results were not corrected for multiple testing in each variant, phenotype and subcategory. This would have required a Bonferroni significance level of P < 0.0023. Although some heterogeneity was present across studies, our finding suggests that 5-HTTLPR, STin2, HTR1A, HTR2A, TPH1 and BDNF may modulate antidepressant response. Molecular Psychiatry (2010) 15, 473-500; doi:10.1038/mp.2008.116; published online 4 November 2008