【摘要】 目的探讨CYP2C19基因多态性与抗精神病药物性肝损害(DILI)的相关性。方法选取单一服用抗精神病药物的166例患者,采用基于传统连接酶检测反应技术(LDR)经过改进后的多重SNP分型技术,对其中符合DILI诊断的DILI组81例与不符合DILI诊断标准的非DILI组85例的CYP2C19基因上的SNP位点rs4244285、rs4986893、rs12248560进行分型,对DILI组及非DILI组间的3个SNPs等位基因和基因型分布频率、单体型进行统计学分析。结果用药后DILI组谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TBIL)均高于非DILI组(P<0.01)。两组间的3个SNPs等位基因和基因型分布频率比较差异无统计学意义(P>0.05)。两组中各代谢型比较差异无统计学意义(P>0.05)。CYP2C19三位点基因型统计学分析发现,DILI组中*1/*3基因分布频率低于非DILI组(P<0.05)。结论 CYP2C19基因三位点基因型中的*1/*3可能会降低抗精神病药物性肝损害的风险,CYP2C19可能是DILI的保护性基因。更多还原

【Abstract】 Objective To analyze the relationship between CYP2C19 genetic polymorphism and drug induced liver injury(DILI) caused by antipsychotics.Methods A total of 166 patients taking single antipsychotics were selected and divided into DILI group(81 cases) and non-DILI group(85 cases).To utilize modified single nucleotide polymorphism(SNP) typing method,based on traditional ligase detection reaction(LDR),to type the SNP gene-locus of rs4244285、rs4986893、rs12248560 in CYP2C19.Performing statistical analysis on allele,genotype distribution frequency and haplotype of three SNPs between DILI group and non-DILI group.Result Levels of ALT,AST,ALP and TBIL in DILI group were all significantly higher than those in non-DILI group(P < 0.01).The three SNPs alleles and genotype distribution frequencies showed no differences between two groups(P > 0.05).There was no difference in each metabolic type between two groups(P > 0.05).Statistic analysis of CYP2C19 three gene-locus genotype showed that the genotype distribution frequency of*1/*3 in DILI group was significantly lower than that in non-DILI group(P < 0.05).Conclusion The*1/*3 of three gene-locus genotype of CYP2C19 may reduce the risk of DILI caused by antipsychotics,and CYP2C19 may be the protective gene of DILI.更多还原