精神分裂症患者多巴胺D1受体基因多态性与抗精神病药疗效的关系

摘要

Objective: To investigate the association of dopamine receptor Dl ( DRD1 ) gene polymorphisms with response of chlorpromazine, risperidone, clozapine treatment in schizophrenia. Method: Used chlorpromazine(n =78) , risperidone(n =90) or clozapine(n= 132) monotherapy for 8 weeks in 300 patients with schizophrenia. The efficacy of antipsychotics was evaluated with positive and negative syndrome scale. DRD1 gene rs265981, rs4532,rs686 and rs265976 polymorphisms were detected with single nucleotide polymorphism technique. Results: The clozapine response group compared to the nonresponse group in total clinical efficacy,distribution of rs265981 genotype T/T,T/C,C/C and allele T,C had statistically significant differences (x2=7.101,F = 0.029; x2 =4.011,P=0.045);rs265976 genotype A/A,A/C,C/C had statistically significant differences(x2=7. 124,P =0. 028) ,but allele A,C had no statistically significant differences(x2=3.54, P = 0. 06). The chlorpromazine response group compared to the nonresponse group in positive symptom, distribution of rs686 allele A,G had statistically significant differences(x2=4. 427 ,P =0. 035) ,but genotype A/A, A/G,G/G had no statistically significant differences ( x2=3. 842, P =0. 146). The clozapine response group compared to the nonresponse group in negative symptom,distribution of rs265976 genotype A/A,A/C,C/C had statistically significant differences ( x2 =5.999,P =0. 05) ,but allele A,C had no statistically significant differences (x2 = 1. 051, P =0. 305). Conclusion: The polymorphisms of DRD1 gene rs265981, rs686 and rs265976 may have important influence on clinical response of antipsychotics on schizophrenias.%目的:探讨精神分裂症患者多巴胺D1受体(DRD1)基因多态性与抗精神病药疗效的关系.方法:300例精神分裂症患者分别给予氯丙嗪(n=78)、利培酮(n=90)、氯氮平(n=132)单一治疗8周；以阳性与阴性症状量表(PANSS)评定疗效；以SNaPshot单核苷酸多态性(SNP)技术检测DRD1基因rs265981、rs4532、rs686和rs265976多态性. 结果:氯氮平总疗效有效组与无效组相比,rs265981基因型T/T、T/C、C/C及等位基因T、C的分布差异有统计学意义(x2=7.101,P=0.029;x2 =4.011,P=0.045)；rs265976基因型A/A、A/C、C/C的分布差异有统计学意义(x2=7.124,P=0.028),但其等位基因A、C的分布差异无统计学意义(x2=3.54,P =0.06).氯丙嗪改善阳性症状有效组与无效组相比,rs686等位基因A、G的分布差异有统计学意义(x2=4.427,P=0.035),但其基因型A/A、A/G、G/G的分布差异无统计学意义(x2=3.842,P=0.146).氯氮平改善阴性症状有效组与无效组相比,rs265976基因型A/A、A/C、C/C的分布差异有统计学意义(x2 =5.999,P=0.05),而其等位基因A、C的分布差异无统计学意义(x2=1.051,P=0.305). 结论:DRD1基因rs265981、rs686和rs265976多态性可能对抗精神病药治疗精神分裂症的临床疗效有着重要影响.