汉族冠心病患者MDR1基因C3435T位点多态性与氯吡格雷抵抗的相关性研究

Correlation between MDR1 gene C3435T polymorphism and clopidogrel resistance in patients with coronary heart disease in Ningxia region

目的探讨宁夏地区汉族人群中,多药耐药基因(MDR1)C3435T位点多态性与冠心病经皮冠状动脉介入治疗(PCI)术后患者发生氯吡格雷抵抗的相关性。方法采集248例研究对象的静脉血,测定二磷酸腺苷(ADP)诱导的血小板聚集率(PAR),根据PAR结果分为氯吡格雷抵抗(CR)组和非氯吡格雷抵抗(NCR)组。应用PCR-RFLP技术检测MDR1基因的C3435T位点核苷酸基因型分布和等位基因频率。结果 C3435T基因可分为CC、CT及TT 3种基因型,在NCR组和CR组中分别占48.3%、41.2%、10.5%和35.5%、32.9%、31.6%,TT基因型的频率在CR组中明显高于NCR组,差异有统计学意义(P<0.05);T等位基因在CR组所占比例明显高于NCR组(48.0%与31.1%,P<0.05)。结论 MDR1基因的C3435T位点TT突变是可能导致宁夏地区汉族人群冠心病PCI术后患者氯吡格雷抵抗发生的因素。

Objective To investigate the correlation between the multidrug resistance gene- 1( MDR1) C3435 T single nucleotide polymorphisms and clopidogrel resistance( CR) in percutaneous coronary intervention( PCI) patients in Ningxia hans population.Methods A total of 248 patients with coronary heart diseases was enrolled. They were divided into CR group and non- CR( NCR)group according to the platelet aggregation rate( PAR). The PAR was detected by optical nephelometry,and PAR ﹥ 50% was defined as CR. The study is a case- control study. Genomic DNA was extracted from the peripheral blood of all patients and Polymerase Chain Reaction( PCR) and Restriction Fragment Length Polymorphism( RFLP) were used to detect the contribution of C3435 T genotypes and alleles. Results The number of CR in this population was 76( 30. 6%). There were 3 kinds of genotypes( CC、CT and TT) of C3435 T and their frequencies in NCR group and CR group were 48. 3% 、41. 2% 、10. 5% and 35. 5% 、32. 9% 、31. 6%. In the two groups,distribution frequency of C3435 T TT genotype and T allele in NCR group was significantly lower than CR group. Further,the difference was statistically significant( P < 0. 05). The genotype frequencies in C3435 T of MDR1 gene conformed well to the Hardy- Weinberg equilibrium in both CR group and NCR group. Conclusion TT genotype of C3435 T gene locus can lead to clopidogrel resistance in PCI patients in Ningxia hans population..