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目的观察急性脑梗死患者氯吡格雷疗效与细胞色素P450 2C19(CYP2C19)基因多态性的关系及其对高敏C-反应蛋白(hs-CRP)的影响。方法入选急性脑梗死患者212例,进行CYP2C19基因检测,按照检测结果分为A、B、C组。A组为快代谢型(*1/*1)87例,B组为中间代谢型(*1/*2,*1/*3)74例和C组为慢代谢型(*2/*2,*2/*3,*3/*3)51例,3组患者均口服首次负荷剂量的氯吡格雷300 mg,每天1次,第2天开始口服氯吡格雷75 mg,每天1次维持治疗。3组患者均连续治疗7 d。比较3组患者的临床疗效、治疗前后的血小板聚集率(PAG)、hs-CRP水平和药物不良反应的发生情况。结果治疗后,A、B、C组的总有效率分别为96.55%(84/87例)、87.84%(65/74例)和78.43%(40/51例),差异有统计学意义(P<0.05)。治疗后,A、B、C组的PAG分别为(29.52±10.60)%,(43.31±10.63)%,(61.67±10.12)%;hs-CRP分别为(1.77±0.54),(2.93±0.68),(4.57±1.03)mg·L-1,与治疗前相比,差异均有统计学意义(P<0.05)。B、C组PAG和hs-CRP与A组相比,差异有统计学意义(P<0.05)。A组出现牙龈出血2例,皮肤黏膜下出血点1例,药物不良反应发生率为3.45%(3/87例);B组出现牙龈出血2例,药物不良反应发生率为2.70%(2/74例);C组出现牙龈出血1例,药物不良反应发生率为1.96%(1/51例)。3组药物不良反应发生率差异无统计学意义(P>0.05)。结论急性脑梗死患者的CYP2C19基因多态性和氯吡格雷的疗效相关,慢代谢型患者的氯吡格雷疗效减弱可能与削弱了药物的抗炎作用有关。
Objective To observe the relationship between the efficacy of clopidogrel and the polymorphism of cytochrome P450 2C19 (CYP2C19) gene in patients with acute cerebral infarction and its effect on high sensitivity C-reactive protein (hs-CRP). Methods A total of 212 patients with acute cerebral infarction were enrolled in this study. CYP2C19 gene was detected and divided into A, B and C groups according to the test results. In group A, there were 87 patients with fast metabolic type (* 1 / * 1), 74 patients with intermediate metabolic type (* 1 / * 2, * 1 / * 3) , 51 patients were given oral administration of the first loading dose of clopidogrel 300 mg once daily and oral clopidogrel 75 mg twice a day for the first 2 days treatment. All the patients in three groups were treated for 7 consecutive days. The clinical efficacy, platelet aggregation rate (PAG), hs-CRP level and adverse drug reactions before and after treatment were compared between the three groups. Results After treatment, the total effective rates in groups A, B and C were 96.55% (84/87), 87.84% (65/74) and 78.43% (40/51), respectively, with significant difference (P <0.05). After treatment, the PAG of group A, B and C were (29.52 ± 10.60)%, (43.31 ± 10.63)% and (61.67 ± 10.12)%, respectively. The hs-CRP were 1.77 ± 0.54 and 2.93 ± 0.68, , (4.57 ± 1.03) mg · L-1, respectively, which were significantly different from those before treatment (P <0.05). Compared with group A, PAG and hs-CRP in group B and group C were significantly different (P <0.05). A group of bleeding gums in 2 cases, subcutaneous mucosal bleeding in 1 case, the incidence of adverse drug reactions was 3.45% (3/87 cases); B group gum bleeding occurred in 2 cases, the incidence of adverse drug reactions was 2.70% (2 / 74 cases). One case of gingival bleeding occurred in group C and the incidence of adverse drug reactions was 1.96% (1/51). There was no significant difference in the incidence of ADR between the three groups (P> 0.05). Conclusion The CYP2C19 gene polymorphism in patients with acute cerebral infarction is related to the efficacy of clopidogrel. The weakened effect of clopidogrel in patients with slow metabolism may be related to the weakened anti-inflammatory effect of the drug.