细胞色素P450 CYP2D6*10B缺陷等位基因与利培酮治疗效应的关系  

Relationship between cytochrome P450 CYP2D6*10B gene and therapeutic effect of risperidone

作　　者：郭晓云 成俊祥[2] 江开达[1] 杨瑞[3] 杨献军[3] 

机构地区：[1]上海交通大学医学院附属精神卫生中心,200032 [2]新乡医学院第二附属医院,453003 [3]新乡医学院,453003

出　　处：《上海精神医学》2010年第1期18-21,共4页Shanghai Archives of Psychiatry

摘　　要：目的探讨CYP2D6*10B缺陷等位基因与利培酮治疗效应的关系。方法采用等位基因的特异性扩增法,根据是否含有突变型CYP2D6*10B缺陷等位基因将70例精神分裂症患者分为野生型等位基因的纯合型(w/w)组(16例),突变型等位基因的纯合型(m/m)组(16例)以及野生型和突变型等位基因的杂合型(m/w)组(38例),观察3组患者利培酮4～6mg/d治疗6周后疗效与不良反应。采用阳性和阴性症状量表(PANSS)评价疗效,副反应量表(TESS)和锥体外系不良反应量表(RSESE)评定药物不良反应。PANSS减分率≥30%为有效。结果治疗6周后,有效者58例。有效组w等位基因频率(0.43)明显低于无效组(0.83),有效组的m等位频率(0.57)明显高于无效组(0.17)。自第4周起,m/w,m/m型PANSS减分值明显多于w/w型。3种基因型患者组间不良反应差异无统计学意义。结论利培酮治疗携带CYP2D6*10B缺陷等位基因患者的疗效优于治疗野生型等位基因患者的疗效。CYP2D6*10B缺陷等位基因与利培酮不良反应无关联。Objective： To investigate relationship between CYP2D6 ＊ 10B mutation genotype and therapeutic effect of risperidone. Methods： Using allele - specific PCR to separate 70 schizophrenia patients into 3 genotypes ： wild type homozygosis （ w/w ） （ 16 cases ） , wild and mutation type heterozygosis （ w/m ） （ 38 cases）, and mutation type homozygosis （m/m） （ 16 eases）. Difference of therapeutic and side effect in patients treated with risperidone 4 - 6 mg/d for 4 weeks were evaluated among three genotypes. Using positive and negative symdrome seale（ PANSS ） to evaluate therapeutic effect every 2 weeks. Using treatment emergent symptom scale （TESS） and rating scale for extrapyramidal side effects （RSESE） to evaluate side effect every week. Response is defined as reduction of PANSS total score ~〉 30%. Results： After 6 - week therapy, 58 patients were rated as responders and 12 patients non - responders. Frequency of w allele was lower in response group （0.43） than in non - response group （0.83） , while frequency of m allele was higher in response group （0.57） than in non- response group （O. 17 ）. Reduction of PANSS score was superior in m/w, m/m group than in w/w group from week 4 of treatment. There was no difference in side effect among 3 genotype groups. Conclusion：Response to risperidone is superior in patients carrying defective CYP2I）6 ＊ 10B allele to wild - type genotype. Defective CYP2D6 ＊ 10B allele does not relate to adverse reactions of risperidone.

关 键 词：精神分裂症 细胞色素P450 CYP2D6 基因型 抗精神病药 治疗结果 

分 类 号：R749.3[医药卫生—神经病学与精神病学]