Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone
Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone
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DOI：
10.1038/sj.tpj.6500211
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发表时间：
2003-12
期刊：
影响因子：
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通讯作者：
Y. Yamanouchi;N. Iwata;Tatsuyo Suzuki;T. Kitajima;M. Ikeda;N. Ozaki
中科院分区：
文献类型：
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作者：
Y. Yamanouchi;N. Iwata;Tatsuyo Suzuki;T. Kitajima;M. Ikeda;N. Ozaki
利培酮是一种广泛使用的非典型抗精神病药，与典型抗精神病药相比具有一定的优势。虽然观察到利培酮治疗效果的变化，但目前还没有确定具体的可预测的标记物。共73例日本精神分裂症患者给予利培酮治疗8周，采用阳性和阴性综合征量表（PANSS）评估临床症状。6个候选多态性（HTR2A−1438G> A、102T> C、H452Y、DRD2−141delC、Taq IA、COMT V158M）进行基因分型。每个个体的双倍型配置用最大似然法估计。采用多元线性回归分析这些单倍型/基因型及其他预后因素对PANSS评分表现的影响。在调整了患者相关变量的影响后，HTR2A二倍型和COMT基因型以及其他潜在的预后因素对临床表现没有显著影响。DRD2单倍型倾向于与更好的临床表现相关。与Ins-A2/Ins-A2二倍型患者（n= 25）相比，Ins-A2/Del-A1二倍型患者（n= 10）的PANSS总分提高40% （P= 0.03）。HTR2A AT/AT双倍型患者（n= 22）的PANSS总分改善程度较AT/GC双倍型患者（n= 33）差15% （P= 0.06）。这些结果应该谨慎对待，因为样本量小，患者过去抗精神病药物使用史的异质性，以及多次校正没有校正的局限性。然而，目前的研究结果在日本精神分裂症患者样本中产生了重要的假设，这可能为未来在其他人群中的药物基因组学研究奠定基础。
Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Six candidate polymorphisms (HTR2A− 1438G> A, 102T> C, H452Y; DRD2− 141delC, Taq IA; COMT V158M) were genotyped. The diplotype configuration for each individual was estimated by the maximum-likelihood method. Multiple linear regressions were used to analyze the effects of these haplotypes/genotype and other prognostic factors on PANSS scale performance. After adjustment for the effects of patient-related variables, HTR2A diplotype and COMT genotype, as well as other potential prognostic factors, did not significantly influence the clinical performance. A DRD2 haplotype tended to correlate with better clinical performance. Compared with patients who had Ins-A2/Ins-A2 diplotype (n= 25), PANSS total scores of patients with Ins-A2/Del-A1 diplotype (n= 10) showed 40% greater improvement (P= 0.03). The PANSS total scores of patients with HTR2A AT/AT diplotype (n= 22) tended to show 15% worse improvement compared with AT/GC diplotype (n= 33)(P= 0.06). These results should be treated with caution because of limitations due to small sample size, heterogeneity of patients with respect to past antipsychotic use history, and no correction for multiple corrections. However, the present findings generate important hypotheses in a sample of Japanese schizophrenia patients that may lay the foundation for future pharmacogenomics investigations in other populations.