Relationship between clopidogrel responsiveness and CYP2C19 genotype by thromboelastography in patients with coronary heart disease after PCI / 中国输血杂志

【Objective】 To explore the relationship between clopidogrel responsiveness and CYP2C19 gene polymorphism by thromboelastography(TEG) after PCI in patients with coronary heart disease, and its guiding significance for the use of clopidogrel after PCI. 【Methods】 A total of 246 patients who underwent PCI surgery in our hospital from June 2018 to May 2021 and routinely took clopidogrel maintenance treatment after the operation were selected.The platelet inhibition rate of the patients was detected by TEG to obtain their response to clopidogrel.The CYP2C19 genotype was detected, and the relationship between the patient′s responsiveness to clopidogrel and the CYP2C19 genotype was analyzed. 【Results】 The CYP2C19 genotypes in 246 patients were fast metabolizer (n=95), intermediate metabolizer (n=104) and slow metabolizer (n=47), with the mean ADP inhibition rate(%) at 46.27±21.41, 40.99±25.53 and 24.77±21.68, respectively.They were divided into clopidogrel resistant group (n=98) and clopidogrel normal response group (n=148). The three groups of patients with different CYP2C19 genotypes had no statistically significant differences in gender composition, age and platelet count (P>0.05), while significant differences in hypertension, diabetes and hyperlipidemia(P0.05), but they were all lower than those with slow metabolism patients (both P0.5). Statistically significant difference was noticed in the low responsiveness to clopidogrel by different CYP2C19 genotypes (P<0.05). The drug responsiveness of clopidogrel measured by TEG had strong correlation with the patient′s CYP2C19 genotype.When the ADP inhibition rate was the best cut-off value (27.10%), the sensitivity and specificity of CYP2C19 genotype being diagnosed as the slow metabolite type, was 73.37% and 70.21%, respectively. 【Conclusion】 The response of clopidogrel after PCI in patients with coronary heart disease is associated with CYP2C19 genotype polymorphism.The use of TEG to detect the ADP inhibition rate of patients has strong predictive effect on CYP2C19 genotype and has guiding significance on antiplatelet therapy in patients with coronary heart disease after PCI.

Correlations of CYP2C19 gene polymorphism with platelet inhibitionrate and clopidogrel low responsiveness / 实用医学杂志

Objeetive To investigate the relationships of CYP2C19 genotype polymorphism with platelet inhibition rate and clopidogrel low responsiveness in patients taking percutaneous coronary intervention (PCI) during perioperative administration of clopidogrel.Methods 404 patients taking clopidogrel after PCI were included from February 2016 to February 2017.They were divided into three groups:fast metaboliszer,moderate metaboliszer and slow metabolizer,according to the CYP2C19 genotype.Platelet inhibition rate induced by adenosine diphosphate (ADP) was detected by thrombelastogram,platelet inhibition rate ＜ 30％ was defined as clopidogrel low responsiveness (CLR) group and the relationships between the three groups were analyzed in view of CYP2C19 genotype and the platelet inhibition rate and the clopidogrel low responsiveness.Results (1) The proportions of the three groups was 45.5％,45.3％ and 9.2％ in the 404 patients,no statistically significant difference among the three groups in general data (age,sex,platelet,hypertension,diabetes mellitus,hyperlipidemia) (P ＞ 0.05).(2) There was no statistically significant difference in the platelet inhibition rate between the three groups (P =0.312).(3) There was no significant difference in the clopidogrel low responsiveness between the three groups (P =0.295),with the fast metabolizer group vs.intermediate metabolizer (P =0.522),the fast metabolizer group vs.the slow metabolizer (P =0.117) and the intermediate metabolizer group vs.slow metabolizer (P =0.255).Conclusion There is no correlation of CYP2C19 genotype with platelet inhibition rate and clopidogrel low responsiveness in patients taking clopidogrel after PCI.Only the detection of CYP2C19 genotype may not accurately predict the antiplatelet aggregative activity of clopidogrel.

Effect of P2Y12 Receptor Inhibitors on ACS patients with CYP2C19 medium-metabolized genotype / 实用医学杂志

Objective To evaluate the changes of platelet aggregation rate and short-term prognosis after the application of colopidgrel with booster doses or replaced by ticagrelor for ACS patients with CYP2C19 medium-metabolized genotype). Method A total of 302 patients with medium-metabolized genotype were randomly divided into colopidgrel group (75 mg/bid) and ticagrelor group (90 mg/bid). Patients in both groups accepted other conventional treatments of coronary heart disease and accompanied diseases. The platelet aggregation rates and platelet inhibition rates were observed before and after the treatment. The incidence of adverse events was followed up within 1 m. Results After one-week treatment, the platelet aggregation rates of the inducement with 5 μmol/L ADP had statistical significance between colopidgrel group and ticagrelor group ( P = 0 . 019 ) and the platelet inhibition rates had statistical significance difference between the two groups (P = 0.000). No severe adverse events occurred within one-month follow-up and 10 dyspnea patients were all in ticagrelor group. Conclusions Compared with booster doses of clopidogrel, ticagrelor presents obvious inhibitory effect on platelet of patients with medium-metabolized of ACS but it increases the incidence of dyspnea.

Analysis of CYP2C19 gene polymorphism among different sex,age,and BMI in the southeast of Henan province / 中国基层医药

Objective To study the frequency of CYP2C19 genotype and allele mutation of cytochrome P450 in the southeast part of Henan province,and to understand the effect of sex,age,body mass index (BMI)on the genetic polymorphism of CYP2C19.Methods Genetic polymorphism analysis of CYP2C19 gene in 161 healthy people in Henan province,using gene chip method,87 male,74 female,aged 26 -82 years old,and BMI 17 -31. Results The experiment,a total of CYP2C19 six different gene mutation type,CYP2C19 1 of (40.4%),CYP2C19*1 /*2 (39.1%),CYP2C19 *2 /*2 (14.9%),CYP2C19 *1 /*3 (3.1%),CYP2C19 *2 /*3 (2.5%), CYP2C19*3 /*3 (0%);allelomorph CYP2C19 * 2 (35.7%),follow (2.8%).87 male wild type homozygous for CYP2C19 1 of (39.1%),allelomorph CYP2C19 * 2 (39.1%),follow (3.1%),74 female wild type homozygous for CYP2C19 1 of (41.9%),and other allelomorph CYP2C19 * 2 (32.3%),follow (2.5%).103 cases were more than or equal to 58 years old wild type homozygous for CYP2C19 1 of (47.6%),allelomorph CYP2C19 * 2 (39.8%),follow (3.7%),58 25 groups of wild -type homozygous for CYP2C19 1 of (37.7%),allelomorph CYP2C19 * 2 (32.9%),follow (1.2%),BMI <25 groups of wild -type homozygous for CYP2C19 1 of (42.4%),and other allelomorph CYP2C19 * 2 (38.5%),follow (4.3%).Conclusion There was no significant difference in the genotype of CYP2C19*2 between the BMI and *3 in the southeast part of Henan province.

Prognosis of patients with unstable angina in PCI adverse events factor analysis and the function of CYP2C19 gene mutations / 中国医师进修杂志

Objective To study the prognosis of patients with unstable angina in PCI adverse events factor analysis,and the function of CYP2C 19 gene mutations.Methods From May 2013 to May 2015,226 cases of PCI postoperative patients,after surgery all took aspirin + clopidogrel maintenance to treat for 1 years,analyzed CYP2C19*1,CYP2C19*2,CYP2C19 *3 genotype with fluorescent polymerase chain reaction (PCR),the patients were followed up for 6 months.According to the result of detection of genotype divided into wild type group (CYP2C19 *1/*1),the mutation of mixed group (CYP2C19 *1/*2 and CYP2C19 *1/*3) group and mutations in pure form group (CYP2C19 *2/*2 and CYP2C19 *3/*3).Observed the occurrence of unstable angina of three groups prognosis.Results The mutation of mixed to form and mutation of pure form had a record of hospital clinical adverse events (61.9％ and 45.3％) was significantly higher risk of wild group (42.4％),with statistical significance (P ＜0.05);Logistic regression analysis of diabetes and CYP2C19 genotype with PCI postoperative patients with unstable angina occurred in hospital records of clinical adverse events had good correlation (R =3.424,P=0.009 and R =5.679,P =0.001).Conclusion The CYP2C19 gene mutations and diabetes patients with unstable angina PCI postoperative prognosis is closely related,the lack of CYP2C19 gene type are more likely to affect the prognosis of unstable angina,provide reliable basis for further research.