Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients

Ruinan Ma ^1* Dong Zhang ¹ Zhizhang Li ¹ Ying Ding ¹ XiaoGuang Zhang ¹ Jie Xue ¹ Dan Zhuoma Ci ¹ Yueying Bai ² Liang Hu ^1* Daizhan Zhou ^1* Yunhua Yue ^1*

• ¹ Department of Neurology, Yangpu Hospital, Tongji University, Shanghai, China
• ² Department of Biology, Morrissey College of Arts and Sciences, Boston College, Chestnut Hill, Massachusetts, United States

Background: Aspirin is a cornerstone medication for acute ischemic stroke (AIS), but its efficacy varies significantly among individuals. This study aimed to develop a pharmacogenetic polygenic response score (PgxRS) to predict the incidence of adverse outcomes in aspirin-treated AIS patients.Methods: We conducted a retrospective study involving 828 AIS patients who received aspirin therapy. Fifteen candidate single nucleotide variants (SNPs) in genes related to aspirin's mechanism of action, transport, metabolism, and platelet function were genotyped. The association between SNPs and the risk of unfavorable prognosis (defined as modified Rankin Scale score >1 at 90 days) was assessed using logistic regression analysis. Multivariable models incorporating SNPs and clinical factors were developed to predict adverse outcomes.Results: The rs1045642 GG genotype in the ABCB1 gene was significantly associated with a lower risk of unfavorable prognosis, while the rs1371097 T allele in the P2Y1 gene was linked to a higher risk. A prediction model incorporating these two SNPs along with clinical variables demonstrated moderate diagnostic accuracy for predicting unfavorable prognosis (AUC=0.78, 95% CI: 0.74-0.81).Our findings suggest that rs1045642 and rs1371097 genotypes contribute to variability in aspirin response among AIS patients. The developed PgxRS, incorporating these SNPs and clinical factors, can potentially aid in risk stratification and guide personalized antiplatelet therapy decisions. However, further validation in larger, diverse cohorts is warranted.