宜昌地区人群CYP2C19和PON1基因型分布与氯吡格雷抵抗风险相关性研究

Correlation between CYP2C19 genotype and PON1 genotype and clopidogrel resistance in patients in Yichang area

目的研究宜昌地区人群CYP2C19和PON1基因型分布与氯吡格雷抵抗风险。方法回顾性选取2018年1-12月在本院就诊并服用氯吡格雷抗血小板治疗的患者266例。采用原位杂交荧光染色分析技术检测患者CYP2C19*2(rs4244285,c.681G>A)、CYP2C19*3(rs4986893,c.636G>A)、CYP2C19*17(rs12248560,c.-806C>T)和PON1(rs662)基因型。结果宜昌地区本院就诊患者CYP2C19*2、*3、*17基因主要以野生型为主,其中CYP2C19*2 GG型占比46.24%,CYP2C19*3 GG型占比87.22%,CYP2C19*17 CC型占比99.35%。PON1基因以GA型为主,占比47.74%。CYP2C19*2的3种基因型在男性和女性间分布不同(P<0.05),女性CYP2C19*2基因突变率显著高于男性(P<0.05)。266例患者中氯吡格雷抵抗风险度≥2患者的占比49.2%,对这部分人群临床药师给予了增加氯吡格雷使用剂量或换为替格瑞洛的用药建议。结论2018年宜昌地区在该院就诊的患者中,49.2%的患者存在氯吡格雷抵抗风险,在抗血小板方案上需要增加氯吡格雷的剂量或者换药。这些患者中,女性CYP2C19*2基因突变率显著高于男性(P<0.05),女性患者氯吡格雷抵抗的风险高于男性,因此,临床在进行治疗时需要重视这类人群的基因分型。

Objective To determine the correlation between CYP2C19 genotypes and PON1 genotypes and clopidogrel resistance in Yichang.Methods Totally 266 patients with clopidogrel antiplatelet therapy from January to December 2018 were selected.The fluorescence in situ hybridization(FISH)was used to detect the clopidogrel metabolism related enzymes CYP2C19*2(rs4244285,c.681G>A)and CYP2C19*3(rs4986893,c.636G>A),CYP2C19*17(rs12248560,c.-806C>T)and PON1(rs662)gene types.Results The distribution of CYP2C19*2,CYP2C19*3,and CYP2C19*17 gene types in Yichang area was mainly wild-type.The frequencies of CYP2C9*2 GG type alleles,CYP2C19*3 GG type alleles and CYP2C19*17 CC type alleles were 46.24%,87.22%and 99.35%.The PON1 gene was dominated by GA type,accounting for 47.74%.There was significant distribution difference in CYP2C19 genotypes between genders and the gene mutation rate of CYP2C19*2 in females was significantly higher than that in males(P<0.05).Of the 266 patients,131(49.2%)had clopidogrel resistance.Clinical pharmacists gave advice to increase the dosage of clopidogrel or to replace it with ticagrelor.Conclusion Among the patients in the hospital in Yichang in 2018,about half of the patients present clopidogrel resistance and need to increase the dose of clopidogrel or change to other drugs in the anti-platelet program.The risk of clopidogrel resistance is higher in female patients than in men.It is necessary to pay attention to the genotyping of such patient groups in clinical treatment.