CYP2C19 Loss‐of‐Function Variants Associated With Long‐Term Ischemic Stroke Events During Clopidogrel Treatment in the Chinese Population

Abstract

This study aims to determine whether CYP2C19 loss‐of‐function (LoF) variants were associated with long‐term ischemic stroke risk in Chinese primary care patients treated with clopidogrel. Patients treated with clopidogrel were ascertained from Chinese electronic medical records linked with a biobank for a retrospective cohort study. Their medical information was examined for the period from January 2018 to December 2021. Two CYP2C19 major loss of function variants (*2:rs4244285 and *3: rs4986893) were genotyped. The clinical outcome was ischemic stroke event. Cox regression analysis was used to evaluate the association between the occurrence of ischemic stroke events and CYP2C19 LoF variants. Covariates included age, gender, body mass index, prior ischemic stroke, transient ischemic attack, hypertension, diabetes mellitus, hyperlipoidemia, smoke status, aspirin use, proton‐pump inhibitor use, and statin use. Of the 1,141 patients included in the clopidogrel therapy cohort, 61.9% carried at least one CYP2C19 LoF variant. During a median follow‐up period of 12 months, 103 patients (9.0%) had an ischemic stroke. After adjusting for other risk factors, carriers of CYP2C19 LoF variants had significantly higher risk of ischemic stroke compared with non‐carriers (hazard ratio: 1.64, 95% confidence interval: 1.06–2.53, P = 0.025). This pharmacogenetic study of clopidogrel provides novel insights into the association between the CYP2C19 LoF variant and long‐term stroke risk. We established that there is still a need for CYP2C19 genotype‐guided personalized antiplatelet therapy in those who have returned to the primary care setting for clopidogrel prescription.

Outdoor walking, genetic predisposition, and the risk of incident osteoporosis among older adults: A prospective large population-based cohort study

“…This cohort is based on a class A tertiary hospital of Kunshan, with the partner university, the Kunshan Health and Family Planning Information Center, primary hospitals, and community health service centers. The data of the Kunshan cohort were from the electronic health records (EHR), which were recruited from the annual health examinations of all older adults in Kunshan [17][18][19]. The genotyoing data were extracted from the residual blood samples after health examination [17][18][19].…”

“…The data of the Kunshan cohort were from the electronic health records (EHR), which were recruited from the annual health examinations of all older adults in Kunshan [17][18][19]. The genotyoing data were extracted from the residual blood samples after health examination [17][18][19]. Kushan's local hospital's research ethics committee approved conducting this investigation, with informed consent obtained from all participating individuals.…”