5-HT2A受体基因多态性与奥氮平疗效的关联研究

Association of 5-HT2A receptor gene polymorphisms with the response to olanzapine in Chinese patients with schizophrenia

目的 探讨广州地区汉族人群中5-HT2A受体A1438G和T102C基因多态性与奥氮平疗效的关系。方法 随机抽取143例精神分裂症患者,奥氮平单药治疗8周。治疗前后以阳性和阴性症状量表（PANSS）评定奥氮平临床疗效,按照PANSS减分率≥50%和〈50%分为有效组和无效组。采用聚合酶链反应-限制性片段长度多态性方法（PCR-RFLP）分析5-HT2A受体基因A1438G和T102C多态性。结果 （1）A1438G和T102C多态位点的基因型和等位基因在有效组和无效组之间分布均差异无显著性（P〉0.05）;（2）治疗前A1438G不同基因型患者的阳性症状分及阴性症状分有显著性差异,携GG片段基因的患者阳性症状分为（22.3±2.9）分,显著低于AA型及AG型患者[（25.1±4.2）分;（25.9±3.6）分],而阴性症状分为（23.4±9.2）分,较AA型及AG型明显高;（3）经8周治疗后,携带AA型患者PANSS总减分率、阳性症状减分率、阴性症状减分率、一般精神病理症状减分率均比AG型和GG型患者减分率高,但差异无显著性;（4）各临床指标、PANSS分值及其减分率在T102C不同基因亚型间均差异无显著性（P〉0.05）。结论 5-HT2A受体A1438G和T102C基因多态性与广东地区汉族人群奥氮平疗效不存在关联,但GG基因型可能与精神分裂症的阴性症状严重程度有正关联,而与阳性症状严重程度成负关联。

Objective To investigate the possible association of 5-HT2A receptor gene A1438G and T102C polymorphisms with the response to olanzapine in Chinese patients with schizophrenia. Methods The recruited one hundred and forty-three schizophrenic patients were treated with olanzapine monotherapy for 8 weeks. The patients were evaluated regarding the clinical improvement using the Positive and Negative Syndrome Scale（PANSS） before and 8 weeks after olanzapine administration, and divided into groups of responders and non-responders according to the PANSS reductive rate. The 5-HT2A receptor gene A1438G and T102C polymorphisms were determined by PCR-restriction fragment length polymorphism （PCR-RFLP）. Results No significant differences in genotype and allele frequencies of Ald38G and C102T polymorphisms in 5-HT2A receptor gene were observed between the responders and non-responders（ P 〉0.05 ） ; the PANSS positive subscale score of pretreatment was sig- nificantly lower in patients with GG genotype （22.3 ± 2.9） than those with AA and AG （25.1 ± 4. 2 and 25.9 ± 3.6 respectively）, however, the negative subscale score is significantly higher in patients with GG genotype（23.4 ± 9.2） than those with AA and AG, after 8 weeks＇ olanzapine treatment, patients with AA genotype have moderate higher PANSS reductive rates compared with those with AG and GG genotypes, but not significantly. There is no difference in PANSS score and its reductive rate among three genotypes of T102C polymorphism. Conclusion Our results showed that 5-HT2A receptor A1438G and C102T gene polymorphisms may not be associated with olanzapine＇ s response in the Han Chinese population in Guangdong district; GG genotype may be positively associated with the severe degree of positive symptoms but reversibly with negative symptoms of schizophrenia.