Department of Cardiology, Medical University of Warsaw, Poland.
J Thromb Haemost. 2011 Nov;9(11):2291-301. doi: 10.1111/j.1538-7836.2011.04482.x.
Decreased platelet responsiveness to acetylsalicylic acid (ASA) reported previously in diabetic patients could be attributed to patient-based, clinical, genetic and cellular factors. The objective of the present study was to investigate the effect of the genomic polymorphism on the platelet reactivity in diabetic patients treated with ASA.
The study cohort consisted of 295 Caucasians with diabetes type 2 who had been taking ASA tablets at the dose of 75 mg per day for at least 3 months for primary or secondary prevention of myocardial infarction (MI). Platelet reactivity analyzes were performed using VerifyNow ASA and PFA-100 assays. Genotyping for the selected 27 single nucleotide polymorphisms (SNPs) within 19 genes was performed using a Sequenom iPLEX platform. The results indicate that the statistically significant differences in platelet reactivity were observed in the PFA-100 assay for SNPs in following genes: TXBA2R (rs1131882), ADRA2A (rs4311994), PLA2G7 (rs7756935) and 9p21.3 (rs10120688) (P = 0.02, P = 0.03, P = 0.02, P = 0.03, respectively, all significance levels corrected for multiple comparisons). When using the VerifyNow ASA test, a weak nominal statistical significance (i.e. before multiple comparison testing) was observed for two SNPs in the GPVI gene: rs1671152 and rs1613662 [P = 0.025 (0.5) for both SNPs, corrected for multiple comparisons test].
The results from the present study suggest that the four analyzed genes may contribute to platelet reactivity measured with the PFA-100 assay in the diabetic population treated with ASA.
先前有报道称，糖尿病患者对乙酰水杨酸（ASA）的血小板反应性降低，这可能归因于患者、临床、遗传和细胞因素。本研究的目的是研究基因组多态性对接受 ASA 治疗的糖尿病患者血小板反应性的影响。
本研究队列包括 295 名服用 ASA 片剂（剂量为 75mg/天）至少 3 个月的 2 型糖尿病白种人，用于心肌梗死（MI）的一级或二级预防。使用 VerifyNow ASA 和 PFA-100 测定法进行血小板反应性分析。使用 Sequenom iPLEX 平台对 19 个基因中 27 个单核苷酸多态性（SNP）进行基因分型。结果表明，在 PFA-100 测定法中，以下基因中的 SNP 观察到血小板反应性的统计学显著差异：TXBA2R（rs1131882）、ADRA2A（rs4311994）、PLA2G7（rs7756935）和 9p21.3（rs10120688）（P=0.02、P=0.03、P=0.02、P=0.03，所有显著性水平均经多重比较校正）。当使用 VerifyNow ASA 测试时，GPVI 基因中的两个 SNP 观察到弱的名义统计学显著性（即，在多重比较测试之前）：rs1671152 和 rs1613662[P=0.025（0.5）对于这两个 SNP，经多重比较测试校正]。
本研究结果表明，在接受 ASA 治疗的糖尿病患者中，分析的四个基因可能导致 PFA-100 测定法测量的血小板反应性。
