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Correlation Between TCM Constitution And Clopidogrel CYP2C19 Gene Polymorphism And Its Prognosis In Patients With Cerebral White Matter Lesions In Cerebral Small Vessel Disease

Posted on:2022-11-24Degree:MasterType:Thesis
Country:ChinaCandidate:F C LiuFull Text:PDF
GTID:2544307295990459Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Objective To explore the correlation between patients with cerebral white matter lesions in cerebral small vessel disease and Chinese medicine constitution by assessing the Chinese medicine constitution of patients with cerebral white matter lesions in cerebral small vessel disease.At the same time,the distribution of CYP2C19*2/*3allele of clopidogrel was tested in ischemic strokepatientswithcerebral white matter lesionsto explore the correlation between the recurrence of cerebrovascular events and the distribution of TCM constitution and CYP2C19*2/*3 gene polymorphism of clopidogrel in patients with cerebral white matter lesions in cerebral small-vessel disease,and then to provide clinical guidance and theoretical support for patients with white matter lesions in the brain of different TCM constitutions.MethodsThis study was a cross-sectional study.Patients with cerebral white matter lesions in cerebral small vessel disease were screened according to inclusion and exclusion criteria.General data of the included patients with cerebral white matter lesions were collected,and the Chinese medicine physical fitness of the included patients was assessed according to the criteria of "Classification and Determination of Chinese Medicine Physical Fitness".The cognitive function of the included patients was assessed using the Simple Mental State Examination Scale(MMSE)and the Montreal Cognitive Assessment Scale(Mo CA).A cohort study was also used to genotype clopidogrel-associated CY92C19 single nucleotide gene polymorphisms in patients with ischaemic strokewith cerebral white matter lesions in cerebral small vessel disease associated,with regular follow-up.The measures in this study were tested for normality distribution,and data that did not satisfy the normality test distribution were expressed as means.The Wilcoxon Mann-Whitney U rank sum test was used for two independent samples.Statistical descriptions of the count data were made using the composition ratio(%),and statistical analyses were performed using the Pearson χ2test,Pearson corrected χ2 test,and Fisher’s exact probability method.Correlations between different TCM body types and blood biochemical indices,and correlations between different TCM body types and clopidogrel CYP2C19 *2/*3 gene polymorphisms were analysed using dichotomous logistic regression.The effects of TCM physical fitness and different risk factors on recurrence of cerebrovascular events in patients with ischaemic stroke with cerebral white matter lesions were analysed by using Cox proportional risk regression.Results1.From May 2017 to February 2021,a total of 373 patients with cerebral small vessel disease cerebral white matter lesions were included in the Department of Cerebral Diseases,Shanghai TCM-Integrated Hospital,of which 194 were male and179 were female.The distribution of TCM constitution showed that there were131cases(35.1%)of pinghe,86 cases(22.1%)of phlegm-damp,85 cases(21.9%)of qi-vacant,77 cases(19.8%)of blood-stasis,64 cases(16.5%)of yang-vacant,60cases(15.4%)of yin-vacant,36 cases(9.3%)of damp-heat,36 cases(9.3%)of qi-yu,and 5 cases(1.3%)of special endowment).Combination of TCM constitution: 132cases(35.4%)of pingxin,102 cases(27.3%)of single biased constitution,94 cases(25.2%)of two biased constitutions,26 cases(7.0%)of three biased constitutions and19 cases(5.1%)of four biased constitutions.Binary logistic regression analysis of the TCM constitution and baseline data of patients with cerebral white matter lesions in cerebral small vessel disease showed that there were statistical differences in age and history of alcohol consumption between patients with and without Damp-Heat quality(p< 0.05);binary logistic regression analysis of past medical history suggested that there were statistical differences between patients with a history of coronary heart disease and Qi deficiency quality(p< 0.05);blood biochemical indexes of Binary logistic regression analysis suggested that there were statistical differences in total cholesterol levels and Low-density lipoprotein cholesterol levels between patients with and without phlegm and dampness(p< 0.05).The Pearson chi-square test for the rating of Chinese medical constitution and the degree of cerebral white matter lesions in patients with cerebral small vessel disease showed that there was a statistically significant difference in the severity of different cerebral white matter hyper-signals in patients with phlegmatic and peaceful cerebral white matter lesions(p< 0.05).the results of the Mann-Whitney U test suggested that the scores of MMSE and Mo CA in patients with cerebral white matter lesions of different constitutions were not statistically significant differences(p> 0.05).2.From May 2017 to February 2021,a total of 65 patients who underwent clopidogrel-associated CYP2C19*2 /*3 single nucleotide polymorphism genotype testing for ischemic stroke with cerebral small vessel disease cerebral white matter lesions were enrolled for follow-up in the Department of Cerebral Diseases,Shanghai Integrated Hospital of Traditional Chinese and Western Medicine.There were 41 male and 24 female cases.The distribution of TCM constitution showed that 34(52.3%)were of Phlegm-Damp,18(27.7%)were of Yin-Deficiency,16(24.6%)were of Blood-Stasis,14(21.5%)were of Yang-Deficiency,11(16.9%)were of Qi-Deficiency,9(13.8%)were of Damp-Heat,7(10.8%)were of Ping-He,and 2(3.1%)were of Extraordinary Endowment.One person(1.5%)was of Qi-yu temperament.Combination of TCM constitution: 31(47.7%)single constitution,34(52.3%)compound constitution.The genotypes and alleles of CYP2C19*2 and CYP2C19*3 loci in this study were in H-W genetic equilibrium(p> 0.05).CYP2C19*3 gene polymorphism distribution: 0cases(0%)of CYP2C19*3(A/A),10 cases(15.38%)of CYP2C19*3(G/A),55 cases(84.62%)of CYP2C19*3(G/G),and mutant type in 15.38%.There was a statistical difference in G/G,A/G,and A/A genotypes between the haematopoietic and non-haematopoietic cerebral white matter lesions in cerebral small vessel disease(p<0.05).The patients included were followed up for 3 years from the time of initial onset and recurrence of cerebrovascular events occurred in 10 patients.The 3-year recurrence rate was 15.4%.Patients recurred in 3,1,2,0,1 and 3 cases at 3 months,6 months,9months,1 year,2 years and 3 years respectively,with cumulative recurrence rates of4.6%,6.2%,9.2%,10.8% and 15.4% respectively,7(70.0%)male and 3(30.0%)female,with a mean age of 68.00±9.39 years,the youngest being 56 years and the oldest 84 years.Cox proportional risk regression analysis revealed that High-density lipoprotein cholesterol was a protective factor for recurrence of cerebrovascular events in ischaemic stroke patients with cerebral white matter lesions in cerebral small vessel disease.There was no statistically significant difference between the TCM constitution and CYP2C19*2 /*3(p> 0.05).Conclusion1.Patients with cerebral white matter lesions in cerebral small vessel disease differ in their TCM constitution distribution,with significant correlations with phlegm-damp and qi-vacant qualities.2.History of coronary heart disease was significantly correlated with patients with cerebral vascular disease cerebral with qi-vacant qualities,total cholesterol level was significantly correlated with patients with cerebral vascular disease cerebral with phlegm-damp,and history of alcohol consumption was significantly correlated with patients with cerebral vascular disease cerebral with damp-heat.3.Cerebral white matter lesions in cerebral small vessel disease are more severe in phlegmatic patients than in non-phlegmatic patients with cerebral white matter hyper-signal.4.Blood stasis in patients with ischaemic stroke with cerebral white matter lesions was significantly correlated with clopidogrel CYP2C19*2 gene polymorphism.5.There was no correlation between the CYP2C19*3 genotype and the Chinese medical constitution in patients with white matter lesions with ischaemic stroke.6.Patients with recurrent cerebrovascular events in cerebral white matter lesions with ischaemic stroke have a predominantly phlegm-damp constitution.7.Recurrence of cerebrovascular events in patients with white matter lesions with ischaemic stroke was not correlated with either TCM constitution or CYP2C19*2/*3gene polymorphisms.
Keywords/Search Tags:TCM Constitution, cerebral small vessel disease, Cerebral white matter lesions, CYP2C19*2/*3 gene polymorphism, Recurrence of cerebrovascular events
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