Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy. 2022

Suli Zhang, and Jinhang Zhu, and Hua Li, and Fengzhen Li, and Bin Zhu, and Tao Li, and Shuxin Fang, and Shengying Qin
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University.

Genetic variation has been considered a major contributor to the high variability in the response to dual antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Recently, incidences of ischemic stroke are increasing rapidly in China. We aimed to evaluate the influence of potential determinants on the response of antiplatelet therapy and adverse events in Chinese ischemic stroke patients receiving clopidogrel-aspirin treatment. Based on the clopidogrel drug response pathway and the coagulation and anticoagulation function, we systematically selected 34 genetic polymorphisms in 12 candidate genes. Three hundred and eight patients were divided into 2 groups according to their degree of inhibition of platelet aggregation. Multivariate analysis was then performed to assess the influence of demographic, clinical and genetic factors on platelet reactivity in Chinese ischemic stroke patients. We found that polymorphisms in CYP2C19 and F2R genes were still significantly associated with platelet reactivity in Chinese ischemic stroke patients (P = 0.037 and 0.015). The newly identified rs168753 in F2R gene may influence the efficacy to clopidogrel-aspirin therapy for ischemic stroke patients. We also found that ischemic stroke patients with low level of inhibition of platelet aggregation had higher risk of recurrent ischemic events (P = 0.001). Together, these results emphasized the necessity of genotype-directed antiplatelet therapy and facilitated to minimize adverse ischemic events.

UI MeSH Term Description Entries
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077144 Clopidogrel A ticlopidine analog and platelet purinergic P2Y receptor antagonist that inhibits adenosine diphosphate-mediated PLATELET AGGREGATION. It is used to prevent THROMBOEMBOLISM in patients with ARTERIAL OCCLUSIVE DISEASES; MYOCARDIAL INFARCTION; STROKE; or ATRIAL FIBRILLATION. Clopidogrel Besilate,Clopidogrel Besylate,Clopidogrel Bisulfate,Clopidogrel Hydrochloride,Clopidogrel Napadisilate,Clopidogrel Sandoz,Clopidogrel, (+)(S)-isomer,Clopidogrel-Mepha,Iscover,PCR 4099,PCR-4099,Plavix,SC 25989C,SC 25990C,SR 25989,Clopidogrel Mepha
D000083242 Ischemic Stroke Stroke due to BRAIN ISCHEMIA resulting in interruption or reduction of blood flow to a part of the brain. When obstruction is due to a BLOOD CLOT formed within in a cerebral blood vessel it is a thrombotic stroke. When obstruction is formed elsewhere and moved to block a cerebral blood vessel (see CEREBRAL EMBOLISM) it is referred to as embolic stroke. Wake-up stroke refers to ischemic stroke occurring during sleep while cryptogenic stroke refers to ischemic stroke of unknown origin. Acute Ischemic Stroke,Cryptogenic Embolism Stroke,Cryptogenic Ischemic Stroke,Cryptogenic Stroke,Ischaemic Stroke,Wake-up Stroke,Acute Ischemic Strokes,Cryptogenic Embolism Strokes,Cryptogenic Ischemic Strokes,Cryptogenic Strokes,Embolism Stroke, Cryptogenic,Ischaemic Strokes,Ischemic Stroke, Acute,Ischemic Stroke, Cryptogenic,Ischemic Strokes,Stroke, Acute Ischemic,Stroke, Cryptogenic,Stroke, Cryptogenic Embolism,Stroke, Cryptogenic Ischemic,Stroke, Ischaemic,Stroke, Ischemic,Stroke, Wake-up,Wake up Stroke,Wake-up Strokes
D001241 Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5) Acetylsalicylic Acid,2-(Acetyloxy)benzoic Acid,Acetysal,Acylpyrin,Aloxiprimum,Colfarit,Dispril,Easprin,Ecotrin,Endosprin,Magnecyl,Micristin,Polopirin,Polopiryna,Solprin,Solupsan,Zorprin,Acid, Acetylsalicylic
D013988 Ticlopidine An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES. 53-32C,Ticlid,Ticlodix,Ticlodone,Ticlopidine Hydrochloride,53 32C,5332C,Hydrochloride, Ticlopidine
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D020521 Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810) Apoplexy,Cerebral Stroke,Cerebrovascular Accident,Cerebrovascular Apoplexy,Vascular Accident, Brain,CVA (Cerebrovascular Accident),Cerebrovascular Accident, Acute,Cerebrovascular Stroke,Stroke, Acute,Acute Cerebrovascular Accident,Acute Cerebrovascular Accidents,Acute Stroke,Acute Strokes,Apoplexy, Cerebrovascular,Brain Vascular Accident,Brain Vascular Accidents,CVAs (Cerebrovascular Accident),Cerebral Strokes,Cerebrovascular Accidents,Cerebrovascular Accidents, Acute,Cerebrovascular Strokes,Stroke, Cerebral,Stroke, Cerebrovascular,Strokes,Strokes, Acute,Strokes, Cerebral,Strokes, Cerebrovascular,Vascular Accidents, Brain
D065731 Cytochrome P-450 CYP2C19 A cytochrome P-450 enzyme subtype that oxidizes several important groups of drugs including many PROTON PUMP INHIBITORS and ANTICONVULSANTS. CYP2C19,CYPIIC19,S-Mephenytoin 4'-Hydroxylase,4'-Hydroxylase, S-Mephenytoin,CYP2C19, Cytochrome P-450,Cytochrome P 450 CYP2C19,P-450 CYP2C19, Cytochrome,S Mephenytoin 4' Hydroxylase

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