CYP2D6和DRD2的药物遗传学标志物对利培酮治疗的泰国自闭症谱系障碍儿童和青少年催乳素反应的影响。
Impact of Pharmacogenetic Markers of CYP2D6 and DRD2 on Prolactin Response in Risperidone-Treated Thai Children and Adolescents With Autism Spectrum Disorders.
作者信息
Sukasem Chonlaphat, Hongkaew Yaowaluck, Ngamsamut Nattawat, Puangpetch Apichaya, Vanwong Natchaya, Chamnanphon Montri, Chamkrachchangpada Bhunnada, Sinrachatanant Ananya, Limsila Penkhae
机构信息
From the *Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University; †Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital, Bangkok; and ‡Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Department of Mental Health Services, Ministry of Public Health, Samut Prakan, Thailand.
出版信息
J Clin Psychopharmacol. 2016 Apr;36(2):141-6. doi: 10.1097/JCP.0000000000000474.
OBJECTIVE
The aim of the study was to identify the impact of pharmacogenetic markers associated with prolactin concentration in risperidone-treated children and adolescents with autism spectrum disorders.
METHODS
One hundred forty-seven children and adolescents with autism, aged 3 to 19 years, received risperidone. The clinical data of patients were recorded from medical records. Prolactin levels were measured by chemiluminescence immunoassay. Three CYP2D6 single nucleotide polymorphisms, CYP2D6*4 (1846G>A), *10 (100C>T), and *41 (2988G>A), 1 gene deletion (*5), and DRD2 Taq1A (rs1800497) polymorphism were genotyped by TaqMan real-time polymerase chain reaction.
RESULTS
The 3 common allelic frequencies were CYP2D6*10 (55.10%), *1 (32.65%), and *5 (6.12%), respectively. Patients were grouped according to their CYP2D6 genotypes. There was no significant correlation between the concentrations of prolactin among the CYP2D6 genotypes. In addition, there were no statistical differences in the prolactin response among the CYP2D6-predicted phenotypes of extensive metabolizer and intermediate metabolizer. The DRD2 genotype frequencies were Taq1A A2A2 (38.77%), A1A2 (41.50%), and A1A1 (19.73%), respectively. There were statistically significant differences in prolactin level of patients among the 3 groups (P = 0.033). The median prolactin level in patients with DRD2 Taq1A A2A2 (17.80 ng/mL) was significantly higher than A1A2 (17.10 ng/mL) and A1A1 (12.70 ng/mL).
CONCLUSIONS
DRD2 Taq1A A2A2 polymorphisms may play a significant role in the hyperprolactinemia- associated with risperidone treatment in children and adolescent with autism spectrum disorder. Many drugs used chronically in psychiatric diseases exert their effects mainly through the dopamine D2 receptor. It is therefore possible that these drugs could alter the expression of any dopamine receptor, thus affecting the pharmacodynamics characteristics and toxicity of drug substrates during pharmacotherapy.
目的
本研究旨在确定与接受利培酮治疗的自闭症谱系障碍儿童和青少年催乳素浓度相关的药物遗传学标志物的影响。
方法
147名3至19岁的自闭症儿童和青少年接受了利培酮治疗。从病历中记录患者的临床数据。通过化学发光免疫分析法测量催乳素水平。通过TaqMan实时聚合酶链反应对三种CYP2D6单核苷酸多态性（CYP2D6*4（1846G>A）、10（100C>T）和41（2988G>A））、1个基因缺失（*5）以及DRD2 Taq1A（rs1800497）多态性进行基因分型。
结果
三种常见等位基因频率分别为CYP2D6*10（55.10%）、1（32.65%）和5（6.12%）。患者根据其CYP2D6基因型分组。CYP2D6基因型之间催乳素浓度无显著相关性。此外，在CYP2D6预测的广泛代谢型和中间代谢型表型中，催乳素反应无统计学差异。DRD2基因型频率分别为Taq1A A2A2（38.77%）、A1A2（41.50%）和A1A1（19.73%）。三组患者的催乳素水平存在统计学显著差异（P = 0.033）。DRD2 Taq1A A2A2基因型患者的催乳素水平中位数（17.80 ng/mL）显著高于A1A2（17.10 ng/mL）和A1A1（12.70 ng/mL）。
结论
DRD2 Taq1A A2A2多态性可能在自闭症谱系障碍儿童和青少年利培酮治疗相关的高催乳素血症中起重要作用。许多长期用于精神疾病的药物主要通过多巴胺D2受体发挥作用。因此，这些药物有可能改变任何多巴胺受体的表达，从而在药物治疗期间影响药物底物的药效学特征和毒性。
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