HTR2A A-1438G/T102C polymorphisms predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients
HTR2A A-1438G/T102C polymorphisms predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients
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DOI：
10.1007/s00213-009-1538-z
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发表时间：
2009-08-01
影响因子：
3.4
通讯作者：
Chen, Chia-Hsiang
中科院分区：
文献类型：
--
作者：
Chen, Shih-Fen;Shen, Yu-Chih;Chen, Chia-Hsiang
阿立哌唑作为多巴胺D2和D3以及5-羟色胺1A受体的部分激动剂，作为5-羟色胺2A受体（HTR 2A）的拮抗剂。由于阿立哌唑作为HTR 2A的拮抗剂，HTR 2A的遗传变异可能在解释阿立哌唑应答的变异性方面很重要。（rs63311/rs6313），在患有急性加重的精神分裂症的中国汉族住院患者中，患者（n = 128）给予4周疗程的阿立哌唑。通过限制性片段长度多态性方法对患者进行HTR 2A A-1438 G/T102 C多态性基因分型。临床因素如性别、年龄、病程、教育程度、诊断亚型和药物剂量也被记录。研究人员使用阳性和阴性综合征量表（PANSS）每两周测量一次精神病理学。采用混合模型回归方法（SAS Proc MIXED）分析遗传和临床因素对阿立哌唑治疗后PANSS表现的影响，发现HTR 2A A-1438 G/T102 C多态性的GG/CC基因型组预测阿立哌唑对阴性症状的反应较差。此外，阿立哌唑剂量、年龄、病程和诊断亚型等临床因素对阿立哌唑治疗后PANSS的表现有影响，提示HTR 2A A-1438 G/T102 C多态性可预测阿立哌唑治疗后精神分裂症患者的阴性症状表现。
Aripiprazole acts as a partial agonist at dopamine D2 and D3 and serotonin 1A receptors and as an antagonist at serotonin 2A receptors (HTR2A). Since aripiprazole acts as an antagonist at HTR2A, genetic variants of HTR2A may be important in explaining variability in response to aripiprazole.This study investigated whether the efficacy of aripiprazole can be predicted by functional HTR2A A-1438G/T102C polymorphisms (rs63311/rs6313) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbated schizophrenia.After hospitalization, the patients (n = 128) were given a 4-week course of aripiprazole. Patients were genotyped for HTR2A A-1438G/T102C polymorphisms via the restriction fragment length polymorphism method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype, and medication dosage were noted as well. The researchers measured psychopathology biweekly, using the Positive and Negative Syndrome Scale (PANSS). A mixed model regression approach (SAS Proc MIXED) was used to analyze the effects of genetic and clinical factors on PANSS performance after aripiprazole treatment.We found that the GG/CC genotype group of HTR2A A-1438G/T102C polymorphisms predicts poor aripiprazole response specifically for negative symptoms. In addition, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype, were found to influence PANSS performance after aripiprazole treatment.The data suggest HTR2A A-1438G/T102C polymorphisms may predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients as modified by clinical factors.