CYP2C19基因多态性与奥氮平所致窦性心动过速关系的研究

Research on the relationship between CYP2C19 gene polymorphism and sinus tachycardia induced by olanzapine

目的探讨CYP2C19基因多态性与奥氮平所致窦性心动过速的相关性。方法选择入院后单一服用奥氮平治疗的精神分裂症患者241例,其中服药后出现窦性心动过速119例(心动过速组),未出现窦性心动过速122例(非心动过速组)。对其CYP2C19基因上的SNP位点rs4244285、rs4986893、rs12248560进行检测分型,分析比较两组间的基因型及等位基因分布情况。结果两组在性别、年龄、病程、用药情况,以及基因频率、等位基因频率的分布方面,经比较差异无统计学意义(P>0.05)。三位点基因型中的*1/*3在心动过速组中的分布频率低于非心动过速组[*1/*1:心动过速组为46例(38.6%),非心动过速组为38例(31.1%);*1/*3:心动过速组为9例(7.6%),非心动过速组为19例(15.6%),95%CI=0.159~0.964,χ^(2)=4.299,P<0.05],差异有统计学意义,*1/*17在心动过速组中未检出,分布频率低于非心动过速组[*1/*1:心动过速组为46例(38.6%),非心动过速组为38例(31.1%);*1/*17:心动过速组为0例,非心动过速组为4例(3.3%),P<0.05],差异有统计学意义。代谢型中超快代谢型在心动过速组中未检出,分布频率低于非心动过速组[广泛代谢型为46例(38.6%),非心动过速组为38例(31.1%);*1/*17心动过速组为0例,非心动过速组为4例(3.3%),P<0.05],差异有统计学意义。结论CYP2C19基因中的*1/*3、*1/*17可能会降低服用奥氮平后出现窦性心动过速的风险,CYP2C19可能与奥氮平所致窦性心动过速具有相关性。

Objective To investigate the correlation between CYP2C19 gene polymorphism and olanzapine-induced sinus tachycardia.Methods A total of 241 patients with schizophrenia who were treated with olanzapine alone after admission were selected,including 119 patients with sinus tachycardia(tachycardia group)and 122 patients without sinus tachycardia(non-tachycardia group).Detection and typing of SNP loci rs4244285,rs4986893 and rs12248560 on CYP2C19 gene were carried out,and the genotype and allele distribution between the two groups were analyzed and compared.Results There were no significant differences in gender,age,course of disease and medication between the two groups(P>0.05).There were no significant differences in the distribution of gene frequency and allele frequency between the two groups(P>0.05).Among 3 gene loci,the distribution frequency of*1/*3 in tachycardia group was lower than that in non-tachycardia group[*1/*1 in tachycardia group(n=46,38.6%)and non-tachycardia group(n=38,31.1%);*1/*3 in tachycardia group(n=9,7.6%),non-tachycardia group(n=19,15.6%),95%CI=0.159-0.964,χ^(2)=4.299,P<0.05],and the difference was statistically significant.*1/*17 was not detected in tachycardia group,and the distribution frequency was lower than that in non-tachycardia group,[*1/*1 in tachycardia group(n=46,38.6%)and non-tachycardia group(n=38,31.1%);*1/*17 in tachycardia group(n=0,0)and non-tachycardia group(n=4,3.3%),P<0.05],and the difference was statistically significant.Ultrarapid metabolizer(UM)was not detected in tachycardia group,and its distribution frequency was lower than that in non-tachycardia group,[extensive metabolizer(EM)(n=46,38.6%),non-tachycardia group(n=38,31.1%);*1/*17 tachycardia group(n=0,0),non-tachycardia group(n=4,3.3%),P<0.05],and the difference was statistically significant.Conclusions*1/*3 and*1/*17 on CYP2C19 gene may reduce the risk of sinus tachycardia after olanzapine administration,and CYP2C19 may be related to olanzapine-induced sinus tachycardia.