Neurogenetics Section, Department of Neuroscience, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada.
Pharmacogenet Genomics. 2010 Apr;20(4):274-6. doi: 10.1097/FPC.0b013e328337ce3e.
Earlier results suggest a minor role of variants in the serotonin 3 receptor (HTR3) subunit genes on antipsychotic treatment outcome of schizophrenia patients. In this study, we further investigated the role of the subunits A and B of the HTR3 receptor using 140 schizophrenia patients taking clozapine for 6 months. We have found significant allelic association of clozapine response with three variants in the HTR3A receptor (rs2276302, rs1062613, rs1150226) although only rs1062613 association remained significant after permutations (permutated P=0.041). Moreover, rs2276302 and rs1062613 have shown nominally significant genotypic association. The two haplotypes composed of rs2276302-rs1062613-rs1150226 were also nominally significant. Taken together, our results suggest that variants in the HTR3A receptor gene can play a role in the treatment outcome of clozapine in schizophrenia patients that are refractory or intolerant of typical antipsychotic therapy. Further studies are necessary to confirm the reported associations.
先前的研究结果表明，5-羟色胺 3 受体（HTR3）亚基基因的变异在精神分裂症患者的抗精神病治疗效果中作用较小。在这项研究中，我们使用 140 名接受氯氮平治疗 6 个月的精神分裂症患者，进一步研究了 HTR3 受体亚基 A 和 B 的作用。我们发现，氯氮平反应与 HTR3A 受体中的三个变异(rs2276302、rs1062613、rs1150226)存在显著的等位基因关联，尽管在置换后(rs1062613 的置换 P=0.041)只有 rs1062613 的关联仍然显著。此外，rs2276302 和 rs1062613 表现出名义上显著的基因型关联。由 rs2276302-rs1062613-rs1150226 组成的两个单倍型也具有显著的名义意义。总之，我们的结果表明，HTR3A 受体基因中的变异可能在对抗精神病药物治疗无效或不耐受的精神分裂症患者的氯氮平治疗效果中起作用。需要进一步的研究来证实所报道的关联。
