Influences of an NR1/2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients  

作　　者：Yi-bei Chen Zi-yi Zhou Guo-min Li Can-xing Xiao Wei-bang Yu Shi-long Zhong Ye-feng Cai Jing Jin Min Huang 

机构地区：[1]Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China [2]Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China [3]Medical Research Center of G uangdong General Hospital, Guangzhou 510080, China

出　　处：《Acta Pharmacologica Sinica》2019年第6期762-768,共7页中国药理学报（英文版）

摘　　要：Pregnane X receptor (PXR) is a member of nuclear receptor subfamily 1 (NR1/2) that is a transcriptional regulator of several metabolic enzymes involved in clopidogrel metabolism. In this study we identified and evaluated the contributions of single nucleotide polymorphisms (SNPs) in NR1/2 and cytochrome P450 (CYP) 2C19 alleles to clopidogrel resistance (CR) and long-term clinical outcomes in acute ischemic stroke (IS) patients. A total of 634 patients with acute IS were recruited, who received antiplatelet medication (clopidogrel or aspirin) every day and completed a 1-year follow-up. The selected SNPs were genotyped, and platelet function was measured. Modified Rankin Scale (mRS) scores and main adverse cardiovascular and cerebrovascular events (MACCE) were noted to assess the prognosis. We showed that SNPs NR1/2 rs13059232 and CYP2C19 alleles (2^*/3^*) were related to CR. SNP NR1I2 (rs13059232) was identified as an independent risk factor for the long-term clinical outcomes in the clopidogrel cohorts (P< 0.001), but similar results were not observed in a matched aspirin cohort (P> 0.05). Our results suggest that NR1/2 variant (rsl3059232) could serve as biomarker for clopidogrel therapy and individualized antiplatelet medications in the treatment of acute IS patients.

关 键 词：acute ISCHEMIC stroke ANTI-PLATELET MEDICATION CLOPIDOGREL ASPIRIN NR1/2 individualized MEDICATION 

分 类 号：R[医药卫生]