AUTHOR=Mo Yijun , Lu Yao , Guo Fei , Wu Aihua , Weng Yuesong 

TITLE=Analysis of CYP2C19 gene polymorphism and influencing factors of pharmacological response of clopidogrel in patients with cerebral infarction in Zhejiang, China

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1020593

DOI=10.3389/fcvm.2023.1020593

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Certain genetic and non-genetic factors may cause damaged platelet inhibition by clopidogrel. We aimed to determine the effect of <italic>cytochrome P4502C19</italic> (<italic>CYP2C19</italic>) polymorphism, along with other clinical factors, on the platelet response to clopidogrel in patients with acute ischemic stroke (AIS).</p></sec><sec><title>Methods</title><p>A total of 214 patients with AIS receiving clopidogrel at a maintenance dose of 75 mg daily admitted to the Ningbo First Hospital between 1 January 2020, and 31 December 2021, were enrolled. Platelet aggregation analysis was performed to determine clopidogrel resistance. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to determine <italic>CYP2C19</italic> genotype. Other laboratory data on complete blood count and biochemical parameters were taken from patient medical files.</p></sec><sec><title>Results</title><p>Among the 214 AIS patients treated with clopidogrel in the Ningbo population, the incidence of clopidogrel resistance was approximately 43.9%, and the distribution of <italic>CYP2C19</italic> genotypes was highest for <italic>CYP2C19(*1/*2)</italic> (43.0%), followed by <italic>CYP2C19 (*1/*1)</italic> (38.8%). The distribution of alleles <italic>*1</italic>, <italic>*2</italic>, <italic>*3</italic>, and <italic>*17</italic> was 62.1, 32.5, 4.9, and 0.5%, respectively. A chi-squared test showed that the gene frequencies of alleles <italic>*2</italic> and <italic>*3</italic> were significantly higher in the clopidogrel-resistant group than in the clopidogrel-sensitive group (<italic>p</italic> &lt; 0.001), and a Mann–Whitney U-test showed that high HCY levels were significantly correlated with clopidogrel resistance (<italic>p</italic> &lt; 0.001). Multi-factor logistic regression analysis demonstrated that mutant heterozygous genotype [OR 2.893; 95% confidence interval (CI) 1.456–5.748; <italic>p</italic> = 0.002], mutant homozygous genotype (OR 4.741; 95% CI 1.828–12.298; <italic>p</italic> = 0.001), and high HCY levels (OR 1.209; 95% CI 1.072–1.362; <italic>p</italic> = 0.002) were significantly associated with clopidogrel resistance.</p></sec><sec><title>Conclusion</title><p>According to our results, carrying the <italic>CYP2C19</italic>*<italic>2/*3</italic> allele and high HCY levels are independent risk factors for clopidogrel resistance after clopidogrel therapy in patients with AIS. These two factors should be considered prior to clopidogrel administration.</p></sec>