2018 年第 9 期 第 13 卷

不同年龄段汉族缺血性脑卒中患者ABCB1基因rs1045642多态性与发生氯吡格雷抵抗的相关性分析

Relation between ABCB1 gene rs1045642 polymorphism and clopidogrel resistance in Han patients with ischemic stroke at different ages

作者：胡畔何志义

英文作者：

单位：110001沈阳，中国医科大学附属第一医院神经内科

英文单位：

关键词：缺血性脑卒中；氯吡格雷抵抗；ABCB1；rs1045642；基因多态性；免疫学

英文关键词：

• 摘要：

• 【摘要】目的    探究ABCB1基因rs1045642多态性与不同年龄段汉族缺血性脑卒中患者发生氯吡格雷抵抗（CR）的相关性。方法    选取2015年3月至2017年6月来中国医科大学附属第一医院收治的缺血性脑卒中且发生CR患者62例作为CR组，按照就诊时间、年龄和性别匹配62例非CR缺血性脑卒中患者作为非CR组。采集2组患者免疫学和血清学相关危险因素进行Logistic回归分析，检测不同年龄段ABCB1基因rs1045642基因型和等位基因频率情况，分析不同基因型与血清炎性因子表达的相关性。结果    多元Logistic回归结果显示，白细胞介素1（IL-1，比值比＝3.35，95%置信区间：2.65～4.31）、肿瘤坏死因子α（TNF-α，比值比＝1.56，95%置信区间：0.38～4.36）和高敏C反应蛋白（hs-CRP，比值比＝3.42，95%置信区间：1.21～7.74）是缺血性脑卒中患者发生CR的独立危险因素（均P＜0.05）。CR组和非CR组ABCB1基因单核苷酸多态位点rs1045642同时存在C/C、C/T、T/T三种基因型，其中CR组T/T基因型频率明显高于非CR组（41.94%比11.29%），且CR组T等位基因频率明显高于非CR组（54.84%比33.06%），差异均有统计学意义（均P＜0.01）。对年龄进行分层可知，CR组中≥60岁患者的T/T基因型频率明显高于＜60岁患者（54.55%比27.59%），且等位基因中C减少，T增加，差异均有统计学意义（均P＜0.05）。CR组T/T基因型患者血清IL-1（r＝0.541，P＝0.032）、TNF-α（r＝0.699，P＝0.014）和hs-CRP（r＝0.921，P＜0.001）均明显高于C/C基因型和C/T基因型者，且均与年龄呈正相关。结论    老年缺血性脑卒中患者ABCB1基因rs1045642的T/T基因型携带者更容易发生CR，且T/T基因型缺血性脑卒中患者血清IL-1、TNF-α和hs-CRP的升高可能是发生CR的免疫学机制。

• 【Abstract】Objective    To investigate the relation between polymorphism of ABCB1 gene rs1045642 and clopidogrel resistance(CR) in Han patients with ischemic stroke at different ages. Methods    From March 2015 to June 2017, 62 ischemic stroke patients with CR admitted to the First Affiliated Hospital of China Medical University were selected as CR group; 62 ischemic stroke patients without CR were matched as NCR group. Immunological and serological risk factors were analyzed through Logistic regression. Frequency and allelic variation of ABCB1 gene rs1045642 genotype were detected in all patients and analyzed among different ages. The correlation between different genotypes and serum inflammatory factors was analyzed through Pearson test. Results    Multivariate Logistic regression showed that interleukin-1(IL-1, odds ratio＝3.35, 95% confidence interval: 2.65-4.31), tumor necrosis factor-α(TNF-α,odds ratio＝1.56, 95% confidence interval: 0.38-4.36) and high-sensitivity C-reactive protein(hs-CRP, odds ratio＝3.42, 95% confidence interval: 1.21-7.74) were independent risk factors of CR in patients with ischemic stroke(all P<0.05). In the CR and NCR groups, the single nucleotide polymorphism rs1045642 of ABCB1 gene was found to be C/C, T/T and C/T. The frequency of T/T genotype in the CR group was significantly higher than that in the NCR group（41.94% vs 11.29%）; the frequency of T allele in the CR group was significantly higher than that in the NCR group（54.84% vs 33.06%）(both P＜0.01). In the CR group, the frequency of T/T genotype in patients≥60 years old was significantly higher than that in patients＜60 years old(54.55% vs 27.59%); the C allele decreased and T allele increased with age(all P＜0.05). Serum levels of IL-1(r＝0.541, P＝0.032), TNF-α(r＝0.699, P＝0.014) and hs-CRP(r＝0.921, P＜0.001) in the T/T genotype were significantly higher than in the C/C and C/T genotype and they were positively correlated with age. Conclusions    Elderly patients with ischemic stroke are more susceptible to CR in the rs1045642 T/T genotype. Elevation of serum IL-1, TNF-α and hs-CRP may be an immunological mechanism of CR.