摘要
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HTPR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。
Objective To investigate the distribution of genotype frequencies of CYP2C19＊ 2 and GPIIIa genetic polymorphisms in Han population of Guang Zhou with coronary heart disease and the impact on the clopidogrel responsiveness. Methods A total of 146 patients confirmed with coronary heart disease（ CHD） by coronary angiography were enrolled,and clopidogrel（ 75 mg 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 normal group. Polymerase chain reaction（ PCR） and DNA sequencing methods were used to detect the genotypes of the G681 A and T1565 C. 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 HTPR and may impact the responsiveness of clopidogrel in Han population of Guangzhou with CHD.
出处
《广东医学》
CAS
北大核心
2015年第9期1356-1359,共4页
Guangdong Medical Journal
基金
国家自然科学基金资助项目(编号:81072932)
