The associations of candidate gene polymorphisms with aspirin resistance in patients with ischemic disease: a meta-analysis

Recently, extensive research has been conducted on the relationship between aspirin gene polymorphisms and aspirin resistance (AR) in patients with ischemic diseases. Among the numerous candidate genes, it remains unclear which ones are significantly associated with AR and could potentially serve as potential biomarkers for genetic testing before aspirin use.

Eligible articles were searched in PubMed, Embase, Cochrane Library, WanFang, CNKI and Sinomed. A cohort study examining the efficacy of aspirin in secondary prevention for patients with ischemic diseases, along with a discussion on genetic polymorphisms and their association with AR, has been included. The Newcastle-Ottawa Scale for assessing the quality of included studies. Odds ratios (OR) with 95% confidence intervals (CI) were used as measures of effect. Subgroup analyses were conducted based on different genotypes with the same genetic polymorphisms, different research regions and types of ischemic diseases.

From 75 eligible articles, 94 candidate gene polymorphisms were analyzed. In the overall analysis, 25 genes were subjected to meta-analysis and 69 genes were systematically described. 23 gene polymorphisms were observed to be significantly associated with AR, including PTGS2(rs20417) (OR = 0.57, 95% CI: 0.44–0.73), ITGA2(rs1126643) (OR = 0.52, 95% CI: 0.29–0.93), and TbXA2R(rs1131882) (OR = 1.54, 95% CI: 1.09–2.18) were obtained from the combined analysis of this study, and 20 genes were systematically described in this study. Further subgroup analyses demonstrated that AA genotype for PTGS1(rs1330344) (OR = 0.56, 95%CI:0.43–0.74), C allele for PTGS1(rs5788) (OR = 0.51, 95%CI: 0.30–0.87) polymorphisms were significantly associated with AR. The polymorphisms of 13 genes, including PTGS1(rs1236913), have been studied only in Asia, GP6(rs1613662) has been studied only in Europe, and the polymorphisms of 5 genes, including ABCB1(rs1045642), showed different correlations with AR in various regions. The individuals with the PTGS1 (rs5788) variant who experienced an ischemic stroke (OR = 0.98, 95%CI: 0.54–1.67) may exhibit an elevated risk of AR compared to those with coronary artery disease (OR = 0.51, 95%CI: 0.3–0.87).

Our meta-analysis indicates that PTGS2(rs20417), ITGA2(rs1126643), and TbXA2R(rs1131882) could be potential genetic biomarkers for AR. Among these, PTGS2 (rs20417) is particularly suggested for individuals in Asia with ischemic diseases before aspirin use, as the GC/CC genotype raises AR risk by 42% compared to GG. ITGA2 (rs1126643) increases AR risk by 48% in Asia with the TC/TC genotype versus CC. However, results for ABCB1(rs1045642) and GP1BA(rs2243093) vary by regions, requiring further research.