CYP2C19 Gene Polymorphism And Steady-state Plasma Concentration Of Correlation Between Clopidogrel Resistance

Objective:To study the correlation between the CYP2C19 gene polymorphism and the drug effect of patients taking clopidogrel after reaching steady state plasma concentration.Methods:The patients with coronary heart disease were selected from the First Affiliated Hospital of Kunming Medical University from November 2015 to February 2016, a total of 72 patients with coronary heart disease were selected in accordance with the inclusion criteria and exclusion criteria.First, PL series of multi parameter platelet function analyzer was used to detect Platelet Maximum Aggregation Rate (MAR) as a baseline, the maximum platelet aggregation rate before patients taking clopidogrel, and then 75mg clopidogrel was administered continuously for 5 days, after clopidogrel reached steady-state plasma concentration, the detection of patients taking clopidogrel after MAR decreased percentage. At the same time, CYP2C19 gene was detected by DNA microarray chip technology, and the concentration of active metabolite of clopidogrel was determined by HPLC method.Based on DNA microarray technology, the genotype of CYP2C19 was detected, and according to the functional loss of the No. 636 and No.681st base pairs of CYP2C19 gene was divided into:fast metabolism group (wild type*1/*1 (681GG/636GG)) and intermediate metabolism group mutation (mixed type*1/*2 (636GG/681GA),*1/*3 (636GA/681GG)), the slow metabolism of group (homozygous mutation*2/*2 (636GG/681AA),*2/*3 (636GA/681GA),*3/*3 (636AA/681GG)), according to the above analysis:the correlation between the CYP2C19 genotype and the concentration of the active metabolite of clopidogrel. According to the MAR difference before and after taking clopidogrel, calculate the platelet aggregation inhibition rate (IPA) is divided into:effective group (IPA is equal to or more than 30%), moderately effective group (IPA> 15% to< 30% range) and ineffective group (IPA is less than or equal to 15%), according to the above mentioned group analysis:correlation between IPA and the concentration of active metabolite of clopidogrel in each group; correlation between IPA and CYP2C19 genotypes in each group.Results:1. CYP2C19 genotype, fast metabolism group efficiency is the highest for 80%. Secondly,12.50% of intermediary metabolism, slow metabolism of 0%, the difference is statistically significant; 2. CYP2C19 genotype, not variation of efficiency was 80%, 8.51% higher than the variation; the difference is statistically significant; 3. Clopidogrel active metabolic product derivatives concentration, effective drug metabolic product concentration (ng/ml) highest for 33.70±4.53, secondly is moderately effective group 21.18±5.68, ineffective group of 10.25±2.47; the difference is statistically significant.4. Active metabolites derivatives as drug concentration, fast metabolism group of drug metabolic product concentration (ng/ml) highest for 33.40±4.52, followed by the intermediate metabolite of 21.18±5.56, slow metabolism group of 9.91±1.97; the difference is statistically significant.Conclusions:1. According to the inhibition rate of platelet aggregation in the three groups, the CYP2C19 genotype in the fast metabolic group in the effective group of the highest proportion, the difference between the groups was statistically significant, the study suggested that the effect of the fast metabolic group is the best; 2. According to the inhibition rate of platelet aggregation in the three groups, the CYP2C19 genotype in the not variation group was the highest in the effective group, the difference between the groups was statistically significant, the study suggested that the effect of the not variation group is the best; 3. According to the inhibition rate of platelet aggregation in the three groups, active metabolite of clopidogrel derivatives concentration was the highest in group of effective, the difference between the groups was statistically significant. The efficacy of clopidogrel can be considered to be related to the concentration of the active metabolite of clopidogrel; 4. According to the CYP2C19 genotype and divided it into three metabolic types group, clopidogrel active metabolite derivant in fast metabolism group of drug metabolites concentration is the highest, between groups differences have statistical significance. The study suggested that the concentration of the active metabolite of clopidogrel is related to the CYP2C19 genotype.