急性脑梗死患者中医体质分型与CYP2C19基因多态性的临床研究

Clinical study on traditional Chinese medicine constitution types and CYP2C19 gene polymorphism in acute cerebral infarction

目的:观察急性脑梗死患者中医体质分型与氯吡格雷CYP2C19基因多态性的相关性。方法:采用横断面研究方法,对符合入选标准的100例急性脑梗死患者进行中医体质评估。采用数字荧光杂交测定CYP2C19的基因型;采用Hardy-Weinberg平衡定律对CYP2C19单核苷酸多态性进行遗传平衡检测;中医体质分型与基因多态性的关系采用二分类logistic回归分析。结果:100例急性脑梗死患者中,阳虚质18例(18%)、阴虚质30例(30%)、气虚质18例(18%)、痰湿质51例(51%)、湿热质14例(14%)、特禀质2例(2%)、血瘀质27例(27%)、气郁质4例(4%)、平和质11例(11%);CYP2C19*2基因多态性分布为CYP2C19*2(A/A,突变纯合子)21例(21%)、CYP2C19*2(A/G,杂合子)33例(33%)、CYP2C19*2(G/G,正常纯合子)46例(46%),突变等位基因频率为0.375;CYP2C19*3基因多态性分布为CYP2C19*3(A/A)1例(1%)、CYP2C19*3(G/A)14例(14%)、CYP2C19*3(G/G)85例(85%),突变等位基因频率为0.08;与A/A基因型相比,急性脑梗死患者CYP2C19*2位点G/G基因型与痰湿质(OR=5.105,95%CI:1.308~19.928,P<0.05)、血瘀质(OR=12.557,95%CI:1.741~90.558,P<0.05)存在相关性。结论:急性脑梗死患者中痰湿质患者最多;氯吡格雷CYP2C19*2位点突变率明显高于CYP2C19*3位点突变率;急性脑梗死患者痰湿质、血瘀质与氯吡格雷CYP2C19*2基因多态性可能存在相关性。

Objective To investigate the correlation between Traditional Chinese medicine(TCM)constitution classification and clopidogrel-related CYP2C19 gene polymorphism of acute cerebral infarction patients.Methods A cross-sectional method was used in this study.Patients with acute cerebral infarction were screened and enrolled according to our inclusion and exclusion criteria.TCM constitution were evaluated in patients with acute cerebral infarction.Digital fluorescence hybridization Technology was used to test genotypes of CYP2C19 and Hardy-Weinberg’s equilibrium was used to examine CYP2C19 gene polymorphism of the patients.Binary logistic regression analysis method was used to explore the relationship between TCM constitution types and clopidogrel-related CYP2C19 gene polymorphism in acute cerebral infarction.Results Among the 100 patients with acute cerebral infarction,18 belong to Yang-deficiency constitution(18 cases,18%),30 Yin-deficiency(30 cases,30%),18 belong to Qi-deficiency constitution(18 cases,18%),51 belong to phlegm-dampness constitution(51 cases,51%),14 belong to damp-heat constitution(14 cases,14%),2 belong to special constitution(2 cases,2%),blood-stasis constitution(27 cases,27%),Qi stagnation constitution(4 cases,4%),and normal constitution(11 cases,11%).The CYP2C19*2 gene polymorphism distribution:CYP2C19*2(A/A,mutant homozygous)(21 cases,21%),CYP2C19*2(A/G,mutant heterozygote)(33 cases,33%),CYP2C19*2(G/G)(normal homozygous)(46 cases,46%).The mutant allele frequency was 0.375.Binary logistic regression analysis showed that compared with A/A genotype,the G/G genotype of CYP2C19*2 in acute cerebral infarction was correlated with phlegm-dampness constitution(OR=5.105,95%CI:1.308-19.928,P<0.05)and blood-stasis constitution(OR=12.557,95%CI:1.741-90.558,P<0.05).Conclusions The proportion of phlegm-dampness constitution is the highest in patients with acute cerebral infarction.The mutation rate of clopidogrel-related CYP2C19*2 was significantly higher than that of CYP2C19*3 clopidogrel-related CYP2C19*2 gene polymorphism might be related to phlegm-dampness constitution and blood-stasis constitution.