Hettige Nuwan C, de Moraes Gustavo H F, Kennedy James L, De Luca Vincenzo
Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Room 2374, Toronto, ON M5S 1A8, Canada.
EEG & Genetics Group, Centre for Addiction & Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Pharmacogenomics. 2016 Feb;17(3):199-208. doi: 10.2217/pgs.15.171. Epub 2016 Jan 18.
In order to administer antipsychotic medication with the most beneficial outcome, the appropriate drug and dose needs to be identified. Though often not considered in pharmacogenetic studies, dosage plays an important role in treatment outcome. This study set out to analyze the association between 109 SNPs and antipsychotic dosage among schizophrenia patients. In a previous study, we tested 134 SNPs in regards to antipsychotic dosage. In the current study, we tested additional markers in the same candidate genes that we investigated in the previous study to confirm our previous findings.
We included 263 participants with schizophrenia spectrum disorders between the ages of 18-75. Each participant was assessed cross-sectionally to collect clinical and antipsychotic treatment information through a semi-structured interview. The antipsychotic dosage for each individual was standardized according to chlorpromazine equivalents (CPZe), defined daily dose, and the percentage of maximum dosage (PM%). For each participant, 109 SNPs from 29 candidate genes were imputed or genotyped using a Customized Illumina Chip.
Polymorphisms in the GABRB1 gene were significantly associated with higher antipsychotic dosage according to CPZe and PM% standardization.
Our analysis suggests that variation in the GABRB1 gene may be significantly associated with antipsychotic dosage according to CPZe and PM% standardization. Antipsychotic dosage remains an integral measure for treatment response that warrants future pharmacogenetic testing and studies with larger sample sizes.
为了使抗精神病药物治疗获得最有益的结果，需要确定合适的药物和剂量。尽管在药物遗传学研究中剂量常常未被考虑，但它在治疗结果中起着重要作用。本研究旨在分析精神分裂症患者中109个单核苷酸多态性（SNP）与抗精神病药物剂量之间的关联。在之前的一项研究中，我们针对抗精神病药物剂量检测了134个SNP。在当前研究中，我们在之前研究中所调查的相同候选基因中检测了额外的标记，以证实我们之前的发现。
我们纳入了263名年龄在18至75岁之间的精神分裂症谱系障碍患者。通过半结构化访谈对每位参与者进行横断面评估，以收集临床和抗精神病药物治疗信息。根据氯丙嗪等效剂量（CPZe）、限定日剂量和最大剂量百分比（PM%）对每位个体的抗精神病药物剂量进行标准化。对于每位参与者，使用定制的Illumina芯片对来自29个候选基因的109个SNP进行推断或基因分型。
根据CPZe和PM%标准化，GABRB1基因中的多态性与较高的抗精神病药物剂量显著相关。
我们的分析表明，根据CPZe和PM%标准化，GABRB1基因的变异可能与抗精神病药物剂量显著相关。抗精神病药物剂量仍然是治疗反应的一项重要指标，值得未来进行药物遗传学检测和更大样本量的研究。
