P-gp表达和MDR-1基因C3435T多态性与急性冠状动脉综合征相关性研究  

Association between P-gp expression and MDR-1 C3435T polymorphism on acute coronary syndrome

作　　者：杨小蓉[1] 李国标[1] 李博维[1] 丁彩屏[1] 

机构地区：[1]广东药学院附属第一医院,广东广州510080

出　　处：《广东药学院学报》2015年第4期535-538,共4页Academic Journal of Guangdong College of Pharmacy

基　　金：广东省科技计划项目(2011B031800050);广东省自然科学基金项目(10151022401000013)

摘　　要：目的通过检测临床急性冠状动脉综合征(acute coronary syndrome,ACS)行经皮冠脉介入手术(percutaneous coronary intervention,PCI)后服用氯吡格雷1年后患者淋巴细胞上P糖蛋白(P-gp)的表达及多耐药基因(Mulitidrug resistance,MDR-1)C3435T的多态性,探讨P-gp表达和C3435T多态性与ACS之间的相关性。方法采用流式细胞计数(FCM)检测53例ACS患者淋巴细胞上P-gp表达,运用RTPCR及测序法检测C3435T多态性。选用31例健康体检者作为对照组。结果 (1)P-gp结果:病例组=(21.03±8.04)%,对照组=(9.76±3.35)%,两组比较差异有统计学意义(P<0.05)。(2)C3435T阳性率:病例组50.9%,对照组41.9%,两组比较差异无统计学意义(P>0.05)。(3)基因型结果:C/C型对照组61.1%,病例组51.9%;T/C型病例组25.9%,对照组16.7%;T/T型两组均为22.2%,病例组与对照组3种基因型率值比较差异均无统计学意义(P>0.05);两组分别组内比较,C/C型与其他2种T/C及T/T型分别相比较,差异有统计学意义(P<0.05)。(4)C3435T各基因型P-gp表达:C/C型病例组(13.66±1.4)%,对照组(10.92±2)%,两组比较差异无统计学意义(P>0.05);T/C型病例组(32.62±2.8)%,对照组(10.32±2)%,两组比较差异有统计学意义(P<0.05);T/T型病例组(15.20±7)%,对照组(10.42±1)%,两组比较差异无统计学意义(P>0.05)。结论 (1)正常人淋巴细胞中有低水平的P-gp表达,长期服用氯吡格雷后的ACS患者P-gp高于健康对照组。(2)C3435T基因多态性频率与ACS无相关关系。(3)C3435T多态性中的T/C基因型P-gp表达可能与临床ACS患者氯吡格雷耐药有相关性,并参与了耐药机制的形成。Objective To explore the association between MDR-1 C3435 T polymorphism and p-glycoprotein（ P-gp） expression on acute coronary syndrome. Methods A total of 84 cases including 53 patients with acute coronary syndrome and 31 healthy individuals were collected. The expression of P-gp on T lymphocytes was analyzed using flow cytometry. Segments of target gene were detected by RT-PCR and sequencing methods. Results（ 1） P-gp detection： the expressions of P-gp were（ 21. 03 ± 16. 04） % and（ 9. 76 ± 3. 35） % in the case and control groups（ P 0. 05）;（ 2） C3435 T positive rate： the positive rates of C3435 T were 50. 9% and 61. 1% in the case and control groups（ P 0. 05）;（ 3） genotype frequencies： there was no statistical difference in the genotypes（ C / C,T / C and T / T） between two groups（ P 0. 05）;（ 4） P-gp expression of genotypes： there was statistical difference in T/C genotype（ P 0.05）,but not in C / C and T / T genotypes between two groups（ P 0. 05）. Conclusion There is statistical difference of P-gp expression between two groups. P-gp expression of T / C genotype is associated with ACS and plays a role in clopidogrel-resisted mechanism.

关 键 词：急性冠状动脉综合征 P糖蛋白 C3435T基因多态性 

分 类 号：R541.4[医药卫生—心血管疾病]