CAJ | 학술논문

目的：探讨 CYP2C19*2（G681A）及 GPⅢa（T1565C）基因多态性在广州地区汉族冠心病人群中的分布情况及对氯吡格雷药效反应性的影响。方法共纳入对象146例，均经冠脉造影证实为冠心病患者并连续服用75 mg/ d 氯吡格雷5 d 以上。根据最大血小板聚集率（MPA）结果判断氯吡格雷药效反应性，≥50%为氯吡格雷治疗后血小板高反应性（HTPR，HTPR 组），＜50%为正常（正常组）。采用聚合酶链反应和基因测序的方法检测患者上述两个位点的基因型，对两组相关的临床指标、基因型、等位基因及不良心血管事件发生率进行分析。结果 CYP2C19*2基因 G681A 多态位点3种基因型在两组间的分布差异有统计学意义（P ＜0.05）。A 等位基因频率在 HTPR 组高于正常组（P ＜0.05），A 等位基因携带者 HTPR 的发生风险显著增加（OR ＝1.91，95% CI 1.091～3.344，P ＜0.05）。经 Binary logistic 回归分析校正了相关的临床指标后，CYP2C19*2基因 G681A 多态性仍与 HT-PR 的发生有关（OR ＝2.837，95% CI 1.246～6.458，P ＜0.05）。GPⅢa 基因 T1565C 位点的多态基因型和等位基因的频率在两组中的分布差异均无统计学意义（P ＞0.05）。结论 CYP2C19*2基因 G681A 多态性与 HTPR 的发生密切相关，其可能影响广州地区汉族冠心病人群氯吡格雷药效反应性。
목적：탐토 CYP2C19*2（G681A）급 GPⅢa（T1565C）기인다태성재엄주지구한족관심병인군중적분포정황급대록필격뢰약효반응성적영향。방법공납입대상146례，균경관맥조영증실위관심병환자병련속복용75 mg/ d 록필격뢰5 d 이상。근거최대혈소판취집솔（MPA）결과판단록필격뢰약효반응성，≥50%위록필격뢰치료후혈소판고반응성（HTPR，HTPR 조），＜50%위정상（정상조）。채용취합매련반응화기인측서적방법검측환자상술량개위점적기인형，대량조상관적림상지표、기인형、등위기인급불양심혈관사건발생솔진행분석。결과 CYP2C19*2기인 G681A 다태위점3충기인형재량조간적분포차이유통계학의의（P ＜0.05）。A 등위기인빈솔재 HTPR 조고우정상조（P ＜0.05），A 등위기인휴대자 HTPR 적발생풍험현저증가（OR ＝1.91，95% CI 1.091～3.344，P ＜0.05）。경 Binary logistic 회귀분석교정료상관적림상지표후，CYP2C19*2기인 G681A 다태성잉여 HT-PR 적발생유관（OR ＝2.837，95% CI 1.246～6.458，P ＜0.05）。GPⅢa 기인 T1565C 위점적다태기인형화등위기인적빈솔재량조중적분포차이균무통계학의의（P ＞0.05）。결론 CYP2C19*2기인 G681A 다태성여 HTPR 적발생밀절상관，기가능영향엄주지구한족관심병인군록필격뢰약효반응성。
Objective To investigate the distribution of genotype frequencies of CYP2C19*2 and GPIIIa genetic polymorphisms in Han population of GuangZhou with coronary heart disease and the impact on the clopidogrel responsive-ness. Methods A total of 146 patients confirmed with coronary heart disease(CHD)by coronary angiography were en-rolled,and clopidogrel(75mg daily)were given for more than 5 days. According to maximum platelet aggregation rate (MPA),patients were divided into the high on - treatment platelet reactivity(HTPR)group(MPA≥50% )and the nor-mal group. Polymerase chain reaction( PCR)and DNA sequencing methods were used to detect the genotypes of the G681A and T1565C. The distributions of the frequencies of genotypes and alleles,the clinical indexes and the incidence of adverse cardiovascular events were analyzed. Results Significant differences in genotype frequencies of CYP2C19*2 (G681A)were observed between the two groups(P < 0. 05). Frequency of A allele was significantly higher in HTPR group than that in normal group(P < 0. 05),and A allele carriers were more likely to develop HTPR(OR = 1. 91,95%CI:1. 091 -3. 344,P <0. 05). According to logistic regression analysis adjusted for the clinical indexes,the CYP2C19*2(G681A)genetic polymorphisms resulted as independent risk factor for HTPR(OR = 2. 837,95% CI:1. 246 - 6. 458, P < 0. 05). There was no significant difference between two groups in the genotype or allele frequency of GPIIIa (T1565C). Conclusion CYP2C19*2(G681A)genetic polymorphisms is closely associated with the occurrence of HT-PR and may impact the responsiveness of clopidogrel in Han population of Guangzhou with CHD.