Xue Mei, Yang Xuesong, Yang Lin, Kou Na, Miao Yu, Wang Mingming, Ren Junhua, Zhao Quanli
Cardiovascular Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Department of Vascular Surgery, The First Hospital Affiliated to Shandong University of Traditional Chinese Medicine, Jinan, China.
Evid Based Complement Alternat Med. 2017;2017:9037094. doi: 10.1155/2017/9037094. Epub 2017 Mar 29.
The identification of single nucleotide polymorphisms (SNPs) related to aspirin resistance (AR) is of great significance for the explanation why some individuals demonstrate an incomplete response to aspirin and for optimizing the antiplatelet therapy strategy. The study was designed to investigate the possible associated genetic markers and clinical factors of AR for Chinese patients with chronic stable angina after PCI and to analyze the association between TXA2, PGI2, hs-CRP level, AR, and gene polymorphisms. Totally 207 chronic stable angina patients who received 100 mg maintenance dose daily of aspirin for more than 7 days were enrolled. The inhibition of platelets was assessed using light transmittance aggregometry. TXB2, 6-keto-PGF1, and hs-CRP were measured by radioimmunoassay. Genotyping was performed using Taqman probe technique (rs5787 and rs5911) and gene sequencing technology (rs3842788). By using binary logistic regression analysis, the impact of clinical and genetic determinants on AR was evaluated. The prevalence of AR and aspirin semiresistance (ASR) was 3.86% and 20.76%, respectively, in Chinese chronic stable angina patients. rs5911 A/C and C/C versus A/A genotype (OR = 5.546, 95% CI = 1.812-11.404), rs3842788 A/G versus G/G genotype (OR = 8.358, 95% CI = 2.470-28.286), and blood stasis syndrome (BSS, OR = 10.220, 95% CI = 4.242-24.621) were associated with AR, but rs5787 variants were all homozygous of G/G genotype. Plasma TXB2 and hs-CRP increased significantly in AR and ASR group, while 6-keto-PGF1 showed no difference, and TXB2 level was significantly higher in carriers of the rs3842788 A/G genotype. According to our results, rs5911 and rs3842788 are proved to be specific genetic markers of AR in Chinese chronic stable angina patients for the first time, and BSS was also proved to be a remarkable determinant for AR. The AR and ASR patients were with increased plasma TXB2 and hs-CRP levels, and the TXB2 level was influenced by the variation of rs3842788 genotype.
鉴定与阿司匹林抵抗（AR）相关的单核苷酸多态性（SNP）对于解释为何一些个体对阿司匹林表现出不完全反应以及优化抗血小板治疗策略具有重要意义。本研究旨在调查中国PCI术后慢性稳定型心绞痛患者AR可能的相关遗传标志物和临床因素，并分析血栓素A2（TXA2）、前列环素（PGI2）、高敏C反应蛋白（hs-CRP）水平、AR和基因多态性之间的关联。共纳入207例接受每日100mg维持剂量阿司匹林治疗超过7天的慢性稳定型心绞痛患者。采用光透射聚集法评估血小板抑制情况。采用放射免疫分析法测定TXB2、6-酮-前列腺素F1α（6-keto-PGF1α）和hs-CRP。使用Taqman探针技术（rs5787和rs5911）和基因测序技术（rs3842788）进行基因分型。通过二元逻辑回归分析，评估临床和遗传决定因素对AR的影响。在中国慢性稳定型心绞痛患者中，AR和阿司匹林半抵抗（ASR）的患病率分别为3.86%和20.76%。rs5911 A/C和C/C基因型与A/A基因型相比（比值比[OR]=5.546，95%置信区间[CI]=1.812 - 11.404）、rs3842788 A/G基因型与G/G基因型相比（OR = 8.358，95%CI = 2.470 - 28.286）以及血瘀证（BSS，OR = 10.220，95%CI = 4.242 - 24.621）与AR相关，但rs5787变异均为G/G纯合基因型。AR和ASR组血浆TXB2和hs-CRP显著升高，而6-keto-PGF1α无差异，rs3842788 A/G基因型携带者的TXB2水平显著更高。根据我们的结果，首次证实rs5911和rs3842788是中国慢性稳定型心绞痛患者AR的特异性遗传标志物，且BSS也是AR的一个显著决定因素。AR和ASR患者的血浆TXB2和hs-CRP水平升高，且TXB2水平受rs3842788基因型变异的影响。
