CYP2C19、ABCB1、PON1基因多态性与氯吡格雷抵抗的关系研究

Relationship Between CYP2C19,ABCB1,PON1 Gene Polymorphism and Clopidogrel Resistance

目的:探讨细胞色素P4502C19(CYP2C19)、三磷酸腺苷结合盒转运体(ABCB1)、对氧磷酶-1(PON1)基因多态性与氯吡格雷抵抗的关系。方法:选取2019年10月—2022年10月广州医科大学附属第二医院收治的急性缺血性脑卒中接受经皮冠状动脉介入治疗(PCI)术后服用氯吡格雷且出现抵抗现象的患者90例作为研究对象,均测定CYP2C19(rs4244285,rs4986893),ABCB1(rs1045642)和PON1(rs662)基因型。统计单核苷酸多态性(SNP)基因型,比较不同CYP2C19基因型别与ABCB1、PON1的关系。结果:CYP2C19基因的*1、*2、*3基因突变率分别为22.22%(20/90)、14.44%(13/90)、7.78%(7/90),其中氯吡格雷抵抗患者的CYP2C19*1/*1野生型样本21例(23.33%);突变型样本69例(76.67%),包括CYP2C19*1/*2or*3突变型杂合子和CYP2C19*2/*2or*3突变型纯合子。ABCB1基因C3435T多态性,基因突变率为54.44%(49/90);PON1基因Q192R为AG多态性,基因突变率为51.11%(46/90)。CYP2C19野生型和突变型的ABCB1基因型CC、CT、TT以及PON1基因型GG、GA、AA比较,差异无统计学意义(P>0.05)。结论:氯吡格雷抵抗不仅与CYP2C19单基因因素有关,同时也受其他多基因相互作用共同导致,而ABCB1基因C3435T多态性、PON1基因Q192R多态性与氯吡格雷抵抗无明显关系。

Objective:To investigate the relationship between cytochrome P4502C19(CYP2C19),ATP-binding cassette transporter superfamily B1(ABCB1),paraoxonase-1(PON1)gene polymorphism and clopidogrel resistance.Methods:A total of 90 patients with acute ischemic stroke who received clopidogrel after percutaneous coronary intervention(PCI)and developed resistance from October 2019 to October 2022 in the Second Affiliated Hospital of Guangzhou Medical University were selected as the study subjects.The CYP2C19(rs4244285,rs4986893),ABCB1(rs1045642)and PON 1(rs662)genotypes were determined in all patients.Single nucleotide polymorphism(SNP)genotype was counted.The relationship of different CYP2C19 genotypes with ABCB1 and PON1 was compared.Results:The mutation rates of*1,*2 and*3 genes of CYP2C19 gene were 22.22%(20/90),14.44%(13/90)and 7.78%(7/90),respectively,among which there were 21 cases of CYP2C19*1/*1 wild-type samples in clopidogrel resistant patients.There were 69 cases of mutant samples(76.67%),including CYP2C19*1/*2or*3 mutant heterozygous and CYP2C19*2/*2or*3 mutant homozygous.For ABCB1 gene C3435T polymorphism,the gene mutation rate was 54.44%(49/90);For PON1 gene Q192R AG polymorphism,the gene mutation rate was 51.11%(46/90).There were no significant differences in CC,CT and TT of ABCB1 genotype and GG,GA and AA of PON1 genotype between CYP2C19 wild type and mutant type(P>0.05).Conclusion:Clopidogrel resistance is not only related to CYP2C19 single gene factors,but also caused by the interaction of other multiple genes,while the polymorphism of ABCB1 gene C3435T and PON1 gene Q192R has no significant relationship with clopidogrel resistance.