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目的探讨吸烟和CYP2C19功能缺失性等位基因交互作用对氯吡格雷抗血小板反应性的影响。方法该研究连续募集2011年9月—2013年9月解放军总医院住院并接受阿司匹林和氯吡格雷双联抗血小板治疗的急性冠脉综合征(ACS)患者。采用光密度比浊法(LTA)测定氯吡格雷治疗前后的血小板聚集率,SnaPshot法检测CYP2C19功能缺失性等位基因变异型。利用单因素和多因素统计方法,分析吸烟和CYP2C19基因型交互作用对氯吡格雷治疗前后的血小板聚集率和治疗期间高血小板反应性(HPR)的影响。结果该研究共纳入500例患者,吸烟组203例(40.6%),非吸烟组297例(59.4%)。在非吸烟组,氯吡格雷治疗后的稳定血小板聚集率在CYP2C19*2携带者(*1/*2:43.24±19.39;*2/*2:53.52±19.88)和非携带者(*1/*1:37.91±19.12)之间差异均有统计学意义(校对后P值分别为P=0.029,P<0.001);而在吸烟组中未见上述差异。非吸烟组中至少一个CYP2C19*2等位基因携带者与非携带者之间的HPR的发生率差异有统计学意义(校正后OR:2.13,95%CI:1.23-3.72,P=0.008),而在吸烟组中未见上述差异(校正后OR:1.41;95%CI:0.65-3.04,P=0.387)。结论吸烟和CYP2C19功能缺失性等位基因的交互作用能够影响ACS患者中氯吡格雷的抗血小板反应性。
Objective To investigate the effect of smoking and CYP2C19 loss-of-function allele on the antiplatelet reactivity of clopidogrel. Methods The study recruited consecutive patients with acute coronary syndrome (ACS) who were hospitalized in PLA General Hospital from September 2011 to September 2013 and were treated with dual antiplatelet therapy with aspirin and clopidogrel. The platelet aggregation rate before and after clopidogrel treatment was measured by optical density nephelometry (LTA). The allelic variants of CYP2C19 deletion were detected by SnaPshot method. Univariate and multivariate statistical methods were used to analyze the effect of smoking and CYP2C19 genotype interactions on platelet aggregation before and after clopidogrel treatment and on platelet reactivity (HPR) during treatment. Results A total of 500 patients were enrolled in this study. There were 203 (40.6%) smokers and 297 (59.4%) nonsmokers. In the non-smoking group, stable platelet aggregation rates after clopidogrel treatment were significantly higher in CYP2C19 * 2 carriers (* 1 / * 2: 43.24 ± 19.39; * 2 / * 2: 53.52 ± 19.88) and non-carriers * 1: 37.91 ± 19.12) (P = 0.029, P <0.001, respectively). However, no difference was found in the smoking group. There were significant differences in the incidence of HPR between at least one CYP2C19 * 2 allele carrier and non-carriers in the non-smoking group (adjusted OR: 2.13, 95% CI: 1.23-3.72, P = 0.008) The above differences were not seen in the smoking group (adjusted OR: 1.41; 95% CI: 0.65-3.04, P = 0.387). Conclusion The interaction of smoking with the CYP2C19 loss-of-function allele can affect the antiplatelet reactivity of clopidogrel in ACS patients.