Research On The Relationship Between CYP2C19 Gene Polymorphism And The Platelet Inhibition In Acute Cerebral Ischemia Stroke Patients

Objective:To investigate the incidence and the related risk factors for clopidogrel Resistance(CR) and the CYP2C19 gene polymorphisms in cerebral ischemia stroke(CIS) patients.And to study the relationship between CYP2C19 gene polymorphism and the platelet aggregation inhibition rate in cerebral ischemia stroke patients. To provide the clinical basis for prevention and treatment of CIS.Methods: 72 patients with CIS were involved in this study after receiving written informed consent from March of 2014 to July of 2014 in the inpatient neurological wards of Tianjin First Center Hospital.After admission, clopidogrel(75 mg/d) were continuously given more than seven days.The reports of age, sex, blood pressure, the past medical history and the history of smoking and drinking were collected.And every patient underwent electrocardiogram, cardiac ultrasound and laboratory tests.Polymerase chain reaction-restriction fragment length polymorphism and Pyrosequencing was used to detect CYP2C19*2 and CYP2C19*3 alleles after seven days, and thrombelastogram was used to detect the platelet aggregation inhibition rate. All statistical analyses were performed using SPSS19 software. P-values ￡ 0.05 were considered significant.Results:1. The study included 72 patients with acute cerebral ischemia stroke.CYP2C19 gene polymorphisms pyrosequencing was used to detect CYP2C19*2(G681A) and CYP2C19*3(G636A) alleles. According to the results, the patients were divided into A group with wild type gene(GG) and B group with mutant gene(GA/AA). 39 cases aged 45 to 87 years in A group included 18 males and 21 females, and their average age was 63.72±10.64 years old; 33 cases aged 51 to 91 was 66.25±8.91 years old. There were no significant differences in age, smoking history, drinking history,lipids and glucose levels in blood and other factors.(all p>0.05).2. 72 patients were divided into resistance group and effective group according to the platelet aggregation inhibition rate by thrombelastogram. The clopidogrel resistance group have 16 patients,and the effective group have 56 patients. Therate of clopidogrel resistance was 22.2%. The average platelet aggregation inhibition rate was(68±11)% in effective group and(23±7)% in resistance group.3. There were no significant differences in hypertension, total cholesterol,homocysteine,glycerin trimyristate, and high density lipoprotein cholesterol(HDL-C) between clopidogrel resistance group and effective group(p>0.05). The levels of low density lipoprotein cholesterol(LDL-C) and glycosylated hemoglobin in the clopidogrel resistance group were significantly higher than those in the clopidogrel sensitive group(p<0.05).4. The average platelet aggregation inhibition rate of group A was(41.35±2.83)% and group B was(31.35±2.91)%. The level of platelet aggregation inhibition rate in group B(GA/AA) was significantly lower than that of group A in ischemia stroke patients(p<0.05).Conclusion:1. Clopidogrel resistance is the result of many factors. The levels of low density lipoprotein cholesterol(LDL-C) and glycosylated hemoglobin are related to CR.2. There is correlation between the platelet inhibition rate and gene polymorphism of CYP2C19 in acute cerebral ischemia stroke patients. The level of platelet inhibition rate of CYP2C19 mutant genotype carriers is lower than that of wild genotype carriers.3. There are CYP2C19 gene polymorphism in acute cerebral ischemia stroke patients. The genotype of GG,GA and AA can be found by detecting the genotype of *2(G681A)and *3(G636A).CYP2C19 mutant genotype carriers may increase the risk of recurrence of ischemic stroke.