Rs5911 and rs3842788 Genetic Polymorphism, Blood Stasis Syndrome, and Plasma TXB2 and hs-CRP Levels Are Associated with Aspirin Resistance in Chinese Chronic Stable Angina Patients.

Mei Xue,Yu Miao,Junhua Ren,Quanli Zhao,Mingming Wang,Xuesong Yang,Na Kou,Lin Yang

doi:10.1155/2017/9037094

Abstract

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-PGF1α, 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-PGF1α 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.

Highlights

Aspirin therapy is the cornerstone for the primary and secondary prevention of cardiovascular diseases, including stable angina pectoris and acute coronary syndrome (ACS) [1]
It is noteworthy that the blood stasis syndrome was proved to be a remarkable determinant for aspirin resistance (AR), with as high as 10.2-fold incidence of AR compared to non-blood stasis syndrome
Plasma high-sensitive C-reactive protein (hs-CRP) level increased significantly in AR and aspirin semiresistance (ASR) group, which was in accordance with the results from Larsen et al [14], who reported that increased levels of hs-CRP were associated with augmented platelet reactivity in Denmark stable high-risk coronary artery disease (CAD) patients receiving aspirin as mono antiplatelet therapy, but no genetic variations in COX-1 or GPIIb were found to be related to hs-CRP level. It is proved for the first time that rs5911 and rs3842788 are independently associated with AR in Chinese chronic stable angina patients, with an increased risk as high as 4.5-fold and 8.3-fold, respectively

Summary

Introduction

Aspirin therapy is the cornerstone for the primary and secondary prevention of cardiovascular diseases, including stable angina pectoris and acute coronary syndrome (ACS) [1]. Many patients still experience cardiovascular events, the phenomenon named as aspirin resistance (AR) [2]. Genetic variation may affect patients’ response to drugs, so there are more and more researches focused on the identification of AR related gene polymorphisms. Since aspirin irreversibly inhibits platelet cyclooxygenase- (COX-) 1 to exhibit antiplatelet effect, the COX-1 gene polymorphisms are one of the foci. Maree et al reported that genetic variability in COX-1 [A-842G, C22T (R8W), G128A (Q41Q, rs3842788), C644A (G213G), and C714A (L237M)] appears to modulate aspirin response in Irish patients (n = 144) with cardiovascular disease [3].

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