Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients
Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients
复制标题
DOI：
10.1159/000094727
复制
发表时间：
2006-01-01
影响因子：
3.2
通讯作者：
Kinoshita, Toshihiko
中科院分区：
文献类型：
--
作者：
Kato, Masaki;Fukuda, Tsuyoshi;Kinoshita, Toshihiko
在本研究中，我们检测了5 -羟色胺2A、3A和3B型受体基因（HTR2A、HTR3A、HTR3B）以及5 -羟色胺转运体启动子区域（SERTPR）多态性的影响，并研究了帕罗西汀和氟伏沙明对临床反应的不同特征。在一项为期6周的随机研究中，共纳入了100名日本复发性抑郁症患者。采用汉密尔顿抑郁量表（HAM-D）评估临床反应，并在每次就诊时评估药物不良反应。SERTPR等位基因为I的患者对SSRIs的应答优于s/s基因型携带者（p = 0.015-0.042），对氟伏沙明的应答更为显著。HTR2A的-1438G/G基因型与对SSRIs的良好反应相关（p = 0.010-0.039），特别是对氟伏沙明，并且与帕罗西汀治疗患者的严重恶心相关（p = 0.013）。HTR3A的178C/C基因型与抗抑郁反应相关（p = 0.022-0.042），在帕罗西汀治疗的患者中更为显著（p = 0.002-0.042）。这些影响是相互独立的。我们重复了SERPTR多态性与对SSRIs的反应相关的发现。我们还发现HTR2A和HTR3A多态性与疗效相关，HTR2A多态性也与药物不良反应相关。此外，这些多态性的影响因SSRI而异，因此可能取决于每种SSRI的特征。版权所有(c) 2006 S. Karger AG，巴塞尔。
In this study, we tested the influence of the serotonin type 2A, 3A and 3B receptor genes (HTR2A, HTR3A, HTR3B) in addition to a polymorphism in the promoter region of the serotonin transporter (SERTPR), and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine. A total of 100 Japanese patients affected by major recurrent depression were enrolled in a randomized 6-week study. The clinical response was evaluated using the Hamilton Rating Scale for Depression (HAM-D), and adverse drug reactions were assessed at each visit. Patients with the I allele of SERTPR showed a better response to SSRIs than s/s genotype carriers (p = 0.015-0.042), more significantly to fluvoxamine. The -1438G/G genotype of HTR2A was associated with a good response to SSRIs (p = 0.010-0.039), especially to fluvoxamine, and significantly with severe nausea in paroxetine-treated patients (p = 0.013).The 178C/C genotype of the HTR3A was associated with an antidepressant response (p = 0.022-0.042), and more significantly in paroxetine-treated patients (p = 0.002-0.042). These effects were independent of one another. We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs. We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy, and the HTR2A polymorphism is also associated with adverse drug reactions. Furthermore, the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI. Copyright (c) 2006 S. Karger AG, Basel.