Pharmacogenomics in Precision Medicine by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9789811538957
Publisher: Springer Singapore

8.2.2 Aspirin

Aspirin is recommended as a first-line antiplatelet drug. Due to its widespread availability, low cost, lack of major adverse effects, and familiarity to both physicians and patients, aspirin is the most commonly used antiplatelet agent worldwide. However, studies have revealed that in certain cases, the platelet function was inadequately inhibited, thereby leading to thrombotic events despite of the standard dose of aspirin, resulting in a range of individual response to aspirin therapy. This phenomenon has been termed aspirin resistance. Studies have observed that 5–65% of patients with ischemic stroke has aspirin resistance. Today, the underlying mechanism of aspirin resistance is still controversial, but it has been argued that genetic factors may be an important factor.

Aspirin inhibits platelet function through platelet cyclooxygenase-1 (COX-1) suppression, ultimately resulting in a decreased amount of TXA2. TXA2 is responsible for activation of platelet aggregation by binding to its specific receptor (TXA2 receptor, encoded by TBXA2R). Therefore, polymorphisms in this pathway may affect response to aspirin therapy. As the primary target of aspirin, COX-1 makes a logical enzyme for pharmacogenetic investigation. Polymorphisms in the COX1 gene, PTGS1, have been associated with variable response of platelet aggregation to aspirin. TXA2 receptor polymorphisms have also been associated with variation in aspirin response. The TBXA2R CC (rs1131882) genotype was found more frequently in the aspirin resistant group (81.8% vs 62.4%) than in the sensitive group and was identified as a risk factor for aspirin resistance (odds ratio = 2.712, 95% CI: 1.080–6.810) with a higher level of AA-induced platelet aggregation [6]. Fujiwara showed that aspirin was less effective for 924T homozygote of a TXA2 receptor and 924T>C (rs4523), suggesting that 924T allele is involved in aspirin resistance. However, there is some discordance in the literature, and others have not found a convincing association of variants and aspirin response [7].

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