细胞色素P450的基因多态性与缺血性脑卒中的相关性研究

Analysis of the association of CYP450 gene polymorphisms with ischemic stroke

目的探讨细胞色素P450(CYP450)的基因多态性与缺血性脑卒中(IS)发病的相关性。方法选取2020年1月至2022年8月于郑州市第七人民医院神经内科就诊的390例IS患者为研究对象,将其纳入病例组;选取同期于本院接受体检的410例健康人纳入对照组。收集受试者的临床资料,包括年龄、性别、身体质量指数(BMI)、吸烟史、实验室检查结果等,采用χ2检验与独立样本t检验对临床资料进行统计学比较,进一步采用多因素非条件Logistic回归分析法,分析影响IS发生的非遗传性独立风险因素。采集受试者的空腹外周血样,用Sanger测序检测CYP2C19基因rs4244285、rs4986893、rs12248560和CYP3A5基因rs776746位点的基因型,使用SNPStats在线软件计算各基因型的频率,分析基因型、显性、隐性和加性模型与IS的相关性。结果病例组受试者的总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、载脂蛋白B(Apo-B)和同型半胱氨酸(Hcy)水平等指标均高于对照组,而高密度脂蛋白(HDL-C)和载脂蛋白A1(Apo-A1)水平等指标均低于对照组,差异均具有统计学意义(P<0.05);多因素非条件Logistic回归分析显示,TC(95%CI=1.13-1.92,P=0.02)、LDL-C(95%CI=1.03-2.25,P=0.03)、Apo-A1(95%CI=1.05-2.08,P=0.04)、Apo-B(95%CI=1.7-4.22,P<0.01)、Hcy(95%CI=1.12-1.83,P=0.04)均为影响IS发生的非遗传性独立风险因素。CYP2C19与CYP3A5基因各位点的多态性与IS发病风险的分析结果显示,CYP2C19基因rs4244285位点的AA基因型、rs4986893位点的AG基因型和A等位基因、CYP3A5基因rs776746位点的GG基因型和G等位基因与IS显著相关,并且rs4244285、rs4986893和rs776746位点分别在隐性/加性模型、显性模型和显性/加性模型中也与IS显著相关。结论TC、LDL-C、Apo-A1、Apo-B及Hcy均可影响IS的发生,CYP2C19与CYP3A5基因多态性与IS密切相关,证实CYP450的基因多态性可增加IS的发病风险,可为临床诊断该病的患者提供更多的依据。

Objective To assess the association of cytochrome P450(CYP450)gene polymorphisms with the occurrence of ischemic stroke(IS).Methods From January 2020 to August 2022,390 IS patients treated at the Zhengzhou Seventh People′s Hospital were enrolled as the study group,and 410 healthy individuals undergoing physical examination during the same period were enrolled as the control group.Clinical data of all subjects were collected,which included age,sex,body mass index(BMI),smoking history and results of laboratory tests.Chi-square test and independent sample t test were used for comparing the clinical data.Multivariate logistic regression analysis was used to analyze the non-hereditary independent risk factors for IS.Fasting blood samples of the subjects were collected,and the genotypes of rs4244285,rs4986893,rs12248560 of the CYP2C19 gene and rs776746 of the CYP3A5 gene were determined by Sanger sequencing.The frequency of each genotype was calculated by using SNPStats online software.The association between the genotype and IS under the dominant,recessive and additive models was analyzed.Results The levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C),apolipoprotein B(Apo-B)and homocysteine(Hcy)of the case group were significantly higher than those of the control group,whilst the levels of high density lipoprotein(HDL-C)and apolipoprotein A1(Apo-A1)were significantly lower(P<0.05).Multivariate Logistic regression analysis showed that TC(95%CI=1.13-1.92,P=0.02),LDL-C(95%CI=1.03-2.25,P=0.03),Apo-A1(95%CI=1.05-2.08,P=0.04),Apo-B(95%CI=1.7-4.22,P<0.01)and Hcy(95%CI=1.12-1.83,P=0.04)were non-genetic independent risk factors for the occurrence of IS.Analysis of the association between the genetic polymorphisms and the risk of IS showed that the AA genotype at rs4244285 of the CYP2C19 gene,the AG genotype and A allele at rs4986893 of the CYP2C19 gene,and the GG genotype and G allele at rs776746 of the CYP3A5 gene were significantly associated with IS.Under the recessive/additive model,dominant model and dominant/additive model,polymorphisms of the rs4244285,rs4986893 and rs776746 loci were also significantly associated with the IS.Conclusion TC,LDL-C,Apo-A1,Apo-B and Hcy can all affect the occurrence of IS,and CYP2C19 and CYP3A5 gene polymorphisms are closely associated with the IS.Above finding has confirmed that the CYP450 gene polymorphisms can increase the risk of IS,which may provide a reference for the clinical diagnosis.