代谢型谷氨酸受体基因的多态性对阿立哌唑疗效的影响
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摘要
目的:探讨阿立哌唑治疗精神分裂症的疗效与代谢型谷氨酸受体-2(m GluR2)基因多态性的关系。方法:选择160例精神分裂症患者为研究组,并选择同期健康志愿者160例为对照组,应用阳性与阴性症状量表(PANSS)、临床总体印象量表-严重程度和改善程度量表(CGI-SI)分别于治疗前和治疗后2、4、8周对研究组患者进行疗效评定。采用DNA测序技术检测上述患者m GluR2基因单核苷酸多态性rs724226和rs1468412的基因型并分组研究,并对精神分裂症患者的谷氨酸受体基因多态性进行关联分析。结果:rs724226基因型的患者PANSS总分从治疗2周起开始显著下降,治疗前后差异有统计学意义(P<0.05或P<0.01);rs1468412的基因型的患者PANSS总分下降不明显,治疗前后差异无统计学意义(P>0.05)。结论:阿立哌唑治疗精神分裂症的疗效可能与谷氨酸受体基因的多态性有关。
Objective: To investigate efficacy of Aripiprazole in treatment of schizophrenia and its relationship with metabotropic glutamate receptor-2( m GluR2) gene polymorphism. Methods: 160 schizophrenic patients were selected as study group,while 160 healthy volunteer at the same period were selected as control group. The efficacies were assessed with the positive and negative symptom scale( PANSS) and the clinical global impression scale-severity of illness( CGI-SI) before and 2,4 and 8 weeks after the treatment. The single nucleotide polymorphism of the m GluR2 gene of the patients with rs724226 and rs1468412 genotype was detected by using DNA sequencing technique,and their relations with the glutamate receptor gene polymorphism were analyzed. Results: The PANSS scores of the patients with rs724226 genotype began to decrease significantly from the 2nd treatment,and the differences with those before the treatment were statistically significant( P < 0. 05 or P < 0. 01). However,the PANSS scores of the patients with rs1468412 genotype had no obvious decrease,and the differences with those before the treatment were not statistically significant( P>0.05). Conclusions: The efficacy of Aripiprazole in the treatment of schizophrenia may be associated with the glutamate receptor gene polymorphism.
Objective: To investigate efficacy of Aripiprazole in treatment of schizophrenia and its relationship with metabotropic glutamate receptor-2( m GluR2) gene polymorphism. Methods: 160 schizophrenic patients were selected as study group,while 160 healthy volunteer at the same period were selected as control group. The efficacies were assessed with the positive and negative symptom scale( PANSS) and the clinical global impression scale-severity of illness( CGI-SI) before and 2,4 and 8 weeks after the treatment. The single nucleotide polymorphism of the m GluR2 gene of the patients with rs724226 and rs1468412 genotype was detected by using DNA sequencing technique,and their relations with the glutamate receptor gene polymorphism were analyzed. Results: The PANSS scores of the patients with rs724226 genotype began to decrease significantly from the 2nd treatment,and the differences with those before the treatment were statistically significant( P < 0. 05 or P < 0. 01). However,the PANSS scores of the patients with rs1468412 genotype had no obvious decrease,and the differences with those before the treatment were not statistically significant( P>0.05). Conclusions: The efficacy of Aripiprazole in the treatment of schizophrenia may be associated with the glutamate receptor gene polymorphism.
引文
[1]王嘉炜,王汉东.代谢性谷氨酸受体5在神经胶质细胞中的研究进展[J].中华神经外科疾病研究杂志,2012,12(5):470-471.
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[4]Chaki S,Hikichi H.Targeting of metabotropic glutamate receptors for the treatment of schizophrenia[J].Curr Pharm Des,2011,17(2):94-102.
[5]Bishop JR,Ellingrod V,Moline J,et al.Association between the polymorphic GRM3 gene and negative symptom improvement during olanzapine treatment[J].schizophr Res,2005,77(2):253-260.
[6]潘雨晴,冯雍,李晓婷,等.谷氨酸受体基因功能多态性与精神分裂症的相关研究[J].临床和实验医学杂志,2012,11(3):225-227.
[7]Eyjolfsson EM,Nilsen LH,Kondziella D,et al.Altered 13C glucose metabolism in the cortico-striato-thalamo-cortical loop in the MK-801 rat model of schizophrenia[J].Cereb Blood Flow Metab,2011,31(3):976-985.
[8]顾颖慧,刘永,纵艳艳,等.GABA受体对谷氨酸受体的调控机制研究[J].山东大学学报:医学版,2010,48(12):56-61.
[9]沈渔邨.精神病学[M].第5版,北京:人民卫生出版社,2010:846-847.
[10]Takeuchi H,Remington G.Improving symptoms and side effects in older patients with schizophrenia with decreasing dopamine D2/3 receptor occupancy following risperidone and olanzapine dose reduction[J].Evid Based Ment Health,2015,18(4):117.
[2]Kinoshita A,Takizawa R,Koike S.Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia:An imaging genetics study using multi-channel near-infrared spectroscopy[J].Prog Neuropsychopharm-acol Biol Psychiatry,2015,1(62):14-21.
[3]于文娟,朱浩,卢卫红,等.MK-801建立谷氨酸功能低下精神分裂症大鼠模型的研究[J].中国神经精神疾病杂志,2011,37(10):621-624.
[4]Chaki S,Hikichi H.Targeting of metabotropic glutamate receptors for the treatment of schizophrenia[J].Curr Pharm Des,2011,17(2):94-102.
[5]Bishop JR,Ellingrod V,Moline J,et al.Association between the polymorphic GRM3 gene and negative symptom improvement during olanzapine treatment[J].schizophr Res,2005,77(2):253-260.
[6]潘雨晴,冯雍,李晓婷,等.谷氨酸受体基因功能多态性与精神分裂症的相关研究[J].临床和实验医学杂志,2012,11(3):225-227.
[7]Eyjolfsson EM,Nilsen LH,Kondziella D,et al.Altered 13C glucose metabolism in the cortico-striato-thalamo-cortical loop in the MK-801 rat model of schizophrenia[J].Cereb Blood Flow Metab,2011,31(3):976-985.
[8]顾颖慧,刘永,纵艳艳,等.GABA受体对谷氨酸受体的调控机制研究[J].山东大学学报:医学版,2010,48(12):56-61.
[9]沈渔邨.精神病学[M].第5版,北京:人民卫生出版社,2010:846-847.
[10]Takeuchi H,Remington G.Improving symptoms and side effects in older patients with schizophrenia with decreasing dopamine D2/3 receptor occupancy following risperidone and olanzapine dose reduction[J].Evid Based Ment Health,2015,18(4):117.