Two common mutations within CYP2C19 affected platelet aggregation in Chinese patients undergoing PCI: a one-year follow-up study.
Zhifu WangZhaohui LiuWenyao WangYuanyuan FuWen ChenWenke LiXue ZhangYida TangZhou ZhouPublished in: The pharmacogenomics journal (2018)
The effect of dual antiplatelet therapy, clopidogrel combined with aspirin, was influenced by CYP2C19 gene mutation and heterogeneity of population. Related studies remained controversial and limited, especially in Chinese. Total 3295 unrelated ACS Chinese patients undergoing percutaneous coronary intervention (PCI) were recruited and followed up to 1 year. Meanwhile, baseline and clinical data were retrieved. CYP2C19*2 and *3 were genotyped by sequencing. Associations of variants and metabolic types with platelet reactivity (PR) were analyzed by a logistic regression model. And, a Cox proportional hazards model was utilized to analyze survival data. Confounders included gender, age, smoking status, dosage of aspirin and clopidogrel, and BMI. It was found that patients with allele A in CYP2C19*2 and *3 were susceptibility to high PR (OR, 95%CI and P values were 1.34, 1.20-1.50, <0.0001 and 1.42, 1.13-1.79, 0.0029, respectively) after taking clopidogrel. The PR increased along with the number of loss of function (LOF) allele increased and did in order of haplotype*1, *2, and *3. This research suggested that LOF alleles and risk haplotypes in CYP2C19 could significantly attenuate the response to clopidogrel, which resulted in platelet aggregation.
Keyphrases
- antiplatelet therapy
- percutaneous coronary intervention
- acute coronary syndrome
- patients undergoing
- st segment elevation myocardial infarction
- st elevation myocardial infarction
- acute myocardial infarction
- coronary artery disease
- coronary artery bypass grafting
- electronic health record
- single cell
- big data
- coronary artery bypass
- weight gain
- body mass index
- mental health
- physical activity
- low dose
- copy number
- gene expression
- cardiovascular disease
- left ventricular
- cardiovascular events
- heart failure
- type diabetes
- drug induced