| Objective: To investigate the distribution characteristics of CYP2C19 gene polymorphism among cerebral infarction patients in Suzhou area,and to explore its correlation with the anti-platelet aggregation effect of clopidogrel,so as to provide genetic basis for clinical medication in this area,and explore the clinical application value of ABCD-GENE score,so as to promote the precise treatment of cerebral infarction patients in this area.Method: A total of 388 patients with cerebral infarction who received 75mg/d clopidogrel continuously for more than 5 days were selected from the neurology department of our hospital from July 2021 to July 2022.CYP2C19 genotype determination and platelet aggregation function detection were performed,and the pharmacoreactivity of clopidogrel was determined according to the results of platelet aggregation function detection.The distribution frequency of CYP2C19 alleles and metabolites was calculated and compared with other regions at home and abroad.The ABCD-GENE score of each patient was calculated based on age,body mass index,chronic kidney disease,diabetes,and genotyping,and the prognosis was compared at 6 months after telephone follow-up.Results: 1.A total of 385 patients with cerebral infarction were enrolled during the study period,including 258 males and 127 females,with an average age of 66.48±12.23 years old.There were 142 cases in the normal metabolite group,243 cases in the mutant group(197 cases in the intermediate metabolite group and 46 cases in the slow metabolite group).There were 266 cases with low ABCD-GENE score and 119 cases with high ABCD-gene score.(3 ultrafast metabolites were not included).2.The main metabolites of CYP2C19 in Suzhou population are intermediate metabolites(51.2%),followed by fast metabolites(36.59%),slow metabolites(11.86%),and ultrafast metabolites(0.77%).The majority of alleles were CYP2C19*1(61.73%),followed by CYP2C19*2(32.99%),CYP2C19*3(4.25%)and CYP2C19*17(1.03%).There was no significant difference in the distribution ratio of CYP2C19 metabolic pattern in Suzhou population compared with that in Anhui Province(Hefei,Bengbu,Wuhu)(P>0.05),but it was not consistent with that in Xinjiang and Zhejiang(P<0.05).There was no significant difference between Suzhou and Hubei,Beijing,Jiangxi,Shaanxi,Yunnan,Shenyang,Chongqing and Guangzhou(P>0.05),while CYP2C19 allele distribution in Suzhou was consistent with gene polymorphism distribution in East Asian population,with no significant difference(P>0.05).The allele distribution was different from that of the United States,central and southern Asia,Latin America,and the Near East,and the difference was statistically significant(P<0.05).3.BMI of the normal metabolic group was lower than that of the poor metabolic group,the difference was statistically significant(P<0.05),but there were no statistically significant differences between the two groups in gender,age,weight,previous history of hypertension,coronary heart disease,diabetes,and the proportion of patients with carotid plaque(P>0.05).Triglyceride and homocysteine in normal metabolizer group were lower than those in poor metabolizer group,and the difference was statistically significant(P<0.05).The platelet count of the normal metabolite group was higher than that of the poor metabolite group,the difference was statistically significant(P<0.05),but there were no statistical differences in laboratory indexes such as high-density lipoprotein,partially activated thrombin time,prothrombin time and FIB between the normal metabolite group and the poor metabolite group(P>0.05).Logistics regression analysis showed that the effects of blood homocysteine and platelet count on the metabolic pattern of CYP2C19 were statistically significant(P<0.05).The ADP-induced platelet aggregation rate(60S),(180S),(300S)and ADP-induced maximum platelet aggregation rate in the normal metabolizer group were lower than those in the poor metabolizer group,and the ADP-induced maximum platelet aggregation rate and ADP-induced platelet aggregation rate(180S)in the fast,intermediate and slow metabolizers had statistical significance(P<0.05).The proportion of poor prognosis in normal metabolic group was lower than that in poor metabolic group,but the difference was not statistically significant(P>0.05).4.BMI,body weight,proportion of diabetes mellitus and NIHSS score in low ABCD GENE score group were lower than those in high ABCD gene score group,the difference was statistically significant(P<0.05);There were no significant differences in gender,age,carotid plaque,coronary heart disease and hypertension between the two groups(P>0.05).The total cholesterol in low group was lower than that in high group,and the difference was statistically significant(P<0.05).High density lipoprotein and D-dimer in low group were higher than those in high group,and the difference was statistically significant(P<0.05).Laboratory indexes of low density lipoprotein,blood glucose,glutamic acid,angiotensin transferase,creatinine,GFR,urea and FIB were not statistically significant between the two groups(P>0.05).There were statistical differences in the distribution proportion of fast,intermediate and slow metabolites between low group and high group(P<0.05).ABCD-GENE score predicted poor prognosis 6 months later with an area under the AUC curve of 0.654.Conclusions: 1.CYP2C19 metabolites in Suzhou population are mainly intermediate metabolites,which are consistent with those in Anhui province,but different from those in Xinjiang and Zhejiang.The distribution of CYP2C19 alleles in Suzhou is basically consistent with the polymorphism distribution of CYP2C19 gene in East Asian population,but different from that in the United States,Oceania,Latin America and other regions,indicating that CYP2C19 gene has ethnic and regional differences.2.Blood homocysteine and platelet count may be related to CYP2C19 metabolites,and CYP2C19 gene polymorphism is correlated with clopidogrel’s antiplatelet aggregation function,but not significantly correlated with 6-month prognosis of patients.3.ABCD-GENE score is an effective risk score,and combining CYP2C19 genotype with clinical risk factors affecting clopidogrel response can predict poor prognosis and ischemic event recurrence in patients. |
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