Serretti Alessandro, Lilli Roberta, Smeraldi Enrico
Department of Psychiatry, Instituto Scientifico H San Raffaele, Vita-Salute University, Fondazione Centro San Raffaele del Monte Tabor, Via Stamira D'Ancona 20, 20127, Milan, Italy.
Eur J Pharmacol. 2002 Mar 8;438(3):117-28. doi: 10.1016/s0014-2999(02)01309-2.
Pharmacogenetics will be of substantial help in the field of affective disorders pharmacotherapy. The possible definition of a genetic liability profile for drug side-effects and efficacy will be of great help in treatments that need weeks to months to be effective. During the last few years, a number of groups have reported possible liability genes. The efficacy and time of onset of selective serotonin reuptake inhibitors have been associated with a polymorphism in the promoter region of the transporter (SERTPR) in many independent studies, while variants at the tryptophan hydroxylase gene, 5-HT2a receptor and G-protein beta3 have been associated with them in pilot studies. Lithium long-term prophylactic efficacy has been associated with SERTPR, TPH and inositol polyphosphate 1-phosphatase variants, though in unreplicated samples. A number of further candidate genes were not associated with these treatments. In conclusion, both acute and long-term treatments appear to be, at least to some extent, under genetic influence and preliminary data have identified possible liability genes.
药物遗传学将在情感障碍药物治疗领域提供实质性帮助。针对药物副作用和疗效的遗传易感性概况的可能定义,对于那些需要数周甚至数月才能起效的治疗将大有裨益。在过去几年中,一些研究团队报告了可能的相关基因。在许多独立研究中,选择性5-羟色胺再摄取抑制剂的疗效和起效时间与转运体(SERTPR)启动子区域的多态性有关,而在初步研究中,色氨酸羟化酶基因、5-HT2a受体和G蛋白β3的变体也与之相关。锂盐的长期预防疗效与SERTPR、TPH和肌醇多磷酸1-磷酸酶变体有关,尽管这些样本尚未得到重复验证。还有一些其他候选基因与这些治疗无关。总之,急性和长期治疗似乎至少在一定程度上受到遗传影响,并且初步数据已经确定了可能的相关基因。