细胞色素P450酶1A2基因多态性与度洛西汀抗抑郁临床疗效的关系

Correlation between polymorphism of cytochrome P450 1A2 gene and antidepressant clinical efficacy of duloxetine

目的 研究细胞色素P450酶1A2（CYP1A2）基因C734A及G-2964A位点多态性与度洛西汀临床疗效的关系.方法 用度洛西汀对223例抑郁症患者进行为期6周的治疗,用汉密尔顿抑郁量表（HAMD）评定疗效,聚合酶链反应扩增及限制性片段长度多态性（PCR-RFLP）检测CYP1 A2基因C734A及G-2964A位点单核苷酸多态性,用单因素方差分析分析两者的关系.结果 （1）223例患者中,C734A突变率为63.64％,G-2964A突变率为26.82％.（2）共计220例患者完成全程治疗.两突变位点联合分析结果表明,高活性组、中间活性组及低活性组在治疗后的HAMD减分率分别为（56.05± 10.13）％、（66.36±8.66）％和（73.82±7.10）％,3组之间两两比较均差异具有统计学意义（均P＜0.01）.结论 CYP1A2基因C734A及G-2964A位点多态性与度洛西汀治疗抑郁症的临床疗效密切相关.

Objective To investigate the relationship between C734A and G-2964A polymorphism of cytochrome P450 1A2 gene and clinical efficacy of duloxetine.Methods 223 patients with depression were treated with duloxetine for six weeks.The clinical efficacy was evaluated with the Hamilton rating scale for depression （HAMD） ;single nucleotide polymorphism （SNP） at position C734A and G-2964A of CYP1A2 gene were identified with restriction fragment length polymorphism（RFLPs） ;then one-way ANOVA was adopted to analyze the relationship between SNP and clinical efficacy.Results （1） In 223 patients,the frequency of allele A at locus 734 was 63.64％,while that of allele A at locus-2964 was 26.82％.（2） 220 patient underwent the whole treating course.The conjoint analysis of two locuses indicated that the decreasing ratio of HAMD score of high-activity group,middle-activity group and low-activity after treatment was （56.05± 10.13） ％,（66.36± 8.66） ％ and （73.82± 7.10） ％ respectively,the differences obtained by pairwise comparison of the three groups were of statistical significance（P＜0.01）.Conclusion There is close relationship between C734A and G-2964A polymorphism of CYP1A2 gene and clinical efficacy of duloxetine in the treatment for depression.