Abstract:
Objective To figure out the regularities of distribution of cytochrome P450-2C19 (CYP2C19) in atherosclerosis obliterans(ASO) patients with arteriosclerosis obliterans after stent implantation, and to define the association between the CYP2C19 genotype and the risk of long-term ischemic events in those who receiving clopidogrel.
Methods A total of 50 selectived patients with ASO after stent implantation (TASC A~C) were included from January 2011 to December 2012. It was used to assess the relation of single nucleotide polymorphisms within genes modulating clopidogrel metabolic activation (CYP2C19*2, *3, *17)using chain termination DNA sequencing method. Doppler ultrasound was used to screen follow-up of 12 months. For difficult cases, CTA and DSA were both used to evaluation of patients with common stent stenosis, which was in order to andlyze age, body mass indeoc, gender, diabetes, hypertension, cerebral infarction, factors of coronary heart disease, smoking history of stent clinical prognosis.
Results The allelic mutation frequencies of CYP2C19*2 and *3 were 48.0%(24/50) and 6.0%(3/50). The frequencies of extensive metaboliers, intermediate metabolizers and poor metabolizers were 48.0(n=24), 44.0%(n=22) and 8.0%(n=4), respectively. Among 50 patients, CYP2C19 genotypes (HR 2.688, 95% CI 1.366-5.288, P=0.004) and smoking (HR 2.430, 95% CI 1.024-5.765, P=0.044) were significant predictors of the primary endpoint. In Kaplan-Meier analysis with the CYP2C19 loss-of-function (LOF) genotype, the CYP2C19 LOF carrier status was associated with an increased rate of ischemic events (P=0.007), compared with non-carriers during a year’s follow-up. However, the effect of the CYP2C19*2 versus the *3 allele on ischemic events did not differ (P>0.05).
Conclusion Among ASO patients treated with clopidogrel after stent implantation, CYPRC19 LOF allele carries have a higher risk of ischemic events, particularly stent thrombosis, than non-noncarriers.
Key words:
Cytochrome P450,
Single nucleotide polymorphisms,
Clopidogrel,
Atherosclerosis obliterans
Ying Zhao, yan Zhou, Lan Zhang, Yinghui Ju, Chunyan Zhang, Wei Guo, Baishen Pan, Daqiao Guo. Association between CYP2C19 genotype and the clinical efficacy of clopidogrel therapy in Chinese patients with arteriosclerosis obliterans after stent implantation[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2015, 03(04): 225-229.