细胞色素P4502D6酶基因多态性与氟西汀临床效应的相关性研究

Correlation between polymorphism of cytochrome P450 2D6 gene and clinical response to fluoxetine

目的 研究中国人P45 0 2D6酶 (CYP2D6 )基因多态性与氟西汀临床效应之间的关系。方法 用氟西汀对 10 8例抑郁患者 (抑郁症 89例 ,精神分裂症后抑郁 7例 ,分裂情感性精神病抑郁型4例 ,强迫性神经症 2例 ,焦虑性神经症 1例 ,抑郁性神经症 4例 ,分裂样精神病 (伴抑郁症状 ) 1例 )进行治疗 ,用汉密尔顿抑郁量表 (HAMD)和治疗中需处理的副反应症状量表 (TESS)评定疗效和副反应 ,用聚合酶链反应 限制性片段长度多态性分析法 (PCR RFLP)分析患者CYP2D6基因型。结果 (1)PCR RFLP分析表明 ,在 10 8例抑郁患者中 ,CYP2D6基因型为wt/wt者 2 6例 ,wt/Ch者 5 5例 ,Ch/Ch者2 6例 ,wt/A者 1例 ,未发现B等位基因。CYP2D6等位基因频率分别为CYP2D6wt(5 0 %) ,CYP2D6Ch(4 9 5 %) ,CYP2D6A(0 5 %)。(2 )入组时 ,不同基因型的患者之间HAMD基础评分的差异无显著性(P >0 0 5 )。经氟西汀治疗 4周和 8周后 ,不同CYP2D6基因型患者的HAMD量表评分比治疗前降低 ,差异均有非常显著性 (P =0 0 0 0 ) ;8周后减分率达 80 %左右 ,而TESS评分较低。在不同基因型的患者之间 ,治疗后的HAMD评分、HAMD减分率及TESS评分的差异均无显著性 (P >0 0 5 )。患者治疗前后的HAMD评分及HAMD减分率、TESS评分等与CYP2D6基因型及CYP2D6突变等?

Objective To study the relationship between polymorphism of cytochrome P450 2D6 (CYP2D6) gene and clinical response to fluoxetine. Methods One hundred and eight depressed patients who treated with fluoxetine were involved in the study. The clinical responses and side effects were measured with the Hamilton rating scale for depression (HAMD) and Treatment Emergent Symptoms Scale (TESS). The CYP2D6 gene was genotyped with PCR-RFLP method. Results (1)PCR-RFLP analysis indicated that there were 26 homozygotes of CYP2D6 wild type allele (wt/wt), 55 heterozygotes of allele wt and Ch (wt/Ch), 26 homozygotes of allele Ch (Ch/Ch), and 1 heterozygote of allele wt and A (wt/A). The allele B was not found in this sample. The allele frequencies were: 50.0% for wild type allele, 49.5% for allele Ch, and 0.5% for allele A. (2)There was no significant difference on the basic HAMD scores among different genotypic patients (P>0.05). After 4- and 8-week treatment with fluoxetine, the HAMD score of all patients decreased significantly (P=0.000), while the TESS score was low. There were no significant differences on the post treatment HAMD score, decreasing ratio of HAMD score and TESS score among patients with different genotype (P>0.05). Conclusion There may be no correlation between the polymorphism of cytochrome P450 2D6 gene and clinical response of fluoxetine.