ABCB1 3435C>T Single Nucleotide Polymorphism is Related to In-Stent Restenosis in Patients with Coronary Artery Disease
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摘要: 目的:探讨多药耐药基因(ABCB1)3435C>T单核苷酸多态性与冠状动脉(冠脉)药物涂层支架术后支架内再狭窄(in stent restenosis,ISR)的相关性。方法:纳入2014-01-2017-12冠脉支架术后的患者714例,复查冠脉造影判定ISR,将患者分为ISR组(82例)和non-ISR组(632例),用PCR-RFLP法检测ABCB1 3435C>T基因型,并分析其在ISR和non-ISR组的分布差异,用Logistic回归分析方法分析ISR的独立危险因素。结果:3435C>T的3种基因型和T等位基因分布频率在ISR组和non-ISR组的差异有统计学意义(P<0.01),T等位基因在non-ISR组的分布比例高于ISR组(P<0.01)。Logistic回归分析显示携带T等位基因和服用钙通道阻滞剂(CCB)与ISR风险降低相关(OR=0.52,95%CI:0.297~0.904,P=0.021;OR=0.47,95%CI:0.255~0.863,P=0.015)。在高血压患者亚组分析中,服用CCB的CT/TT型患者ISR发生率显著低于服用CCB的CC基因型患者(4.8%:15.8%,P=0.002);未服用CCB的两组基因型间ISR发生率差异无统计学意义。结论:CCB与携带ABCB1T等位基因高血压患者的ISR风险相关,机制可能与T等位基因降低P糖蛋白表达水平和CCB抑制P糖蛋白活性有关。Abstract: Objective: To explore the effect of ABCB1 3435C>T single nucleotide polymorphism (SNP) on in-stent restenosis (ISR) in patients after coronary drug-eluting stent (DES) implantation.Method: We analyzed data from 714 patients who were implanted with DES from January 2013 to December 2017.ISR was detected by coronary angiography (CAG).The 3435C>T genotypes were identified by PCR-RFLP method and their distribution between ISR and non-ISR group was compared by Chi-square test.A logistic regression model was used to analyze the independent risk factors of ISR.Result: The patients were assigned into ISR and non-ISR group by CAG, with 82 and 632 cases respectively.The distribution of the genotypes and T allele frequency showed difference between groups (P<0.01).The T allele frequency was higher in non-ISR group than that in ISR group (P<0.01).The logistic regression model showed decreased ISR risk by carrying T alleles (OR=0.52, P=0.021) and taking CCB (OR=0.47, P=0.015).The analysis of genotypesubgroup revealed lower ISR risk in patients taking CCB with CT/TT genotype (P<0.01) as compared with CC genotype.However, the ISR risk showed no difference in patients without taking CCB between CT/TT and CC genotype.Conclusion: Taking CCBs is correlated with lower ISR risk in hypertension patients with ABCB1 T alleles.The mechanism may associate with inhibition of P-glycoprotein activity by CCB and lower P-glycoprotein expression level in T allele carriers.
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