背景:氯吡格雷已成为缺血性卒中主要的抗血小板药物,能抑制二磷酸腺苷(ADP)诱导的血小板聚集。P-糖蛋白(P-gp)多药耐药-1(MDR1)是肠细胞中的跨膜外排转运蛋白,在氯吡格雷吸收中起重要作用,因此可能影响血小板聚集。P-gp由ABCB1基因编码。本研讨旨在评价ABCB1多态性对缺血性脑卒中患者氯吡格雷反响变异性的影响及其基因型频率。
方法:对2020年至2023年在RSUI/RSCM中接受氯吡格雷治疗的缺血性卒中患者进行了横断面研究。评估所有受试者的ABCB1多态性C3435T和C1236T。使用VerifyNowPRU测量血小板聚集。氯吡格雷反应变异性被分类为无反应(>208PRU),响应式(95-208PRU),出血风险(<95PRU)。
结果:参加本研究的124名受试者,12.9%的受试者被归类为无反应/耐药,响应率为49,5%,和41,9%的出血风险。ABCB1C1236T纯合子野生型(CC)的出血风险比其他变体高3,76倍(p=0,008;95CI1,41-10,07)。ABCB1C3435T纯合子野生型的基因型频率,杂合子,纯合子变异为35,9%,43,5%和16,9%,ABCB1C1236T基因型频率分别为17,8%,39,5%,和42,7%,分别。
结论:ABCB1C1236T纯合子野生型与其他变体的3,76倍的出血风险相关。ABCB1C1236T最常见的基因型频率是纯合子变异;而ABCB1的C3435T是杂合子。
BACKGROUND: Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the
ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency.
METHODS: A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for
ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95-208 PRU), and bleeding risk (< 95 PRU).
RESULTS: 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk.
ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 - 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of
ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively.
CONCLUSIONS: ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of
ABCB1 C1236T was homozygote variant; while for
ABCB1 C3435T was heterozygote.