Clopidogrel metabolism related gene polymorphisms in Chinese patients with acute coronary syndrome / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes (CYP2C19, ABCB1 and PON1) in Chinese patients with acute coronary syndrome (ACS) by genotype analysis.</p><p><b>METHODS</b>Genetic analysis was performed in patients admitted to Fuwai Hospital from 2005 to 2008 with ACS within 4 weeks. The detection of polymorphisms was performed by TaqMan real-time PCR method. The alleles genotyped were CYP2C19 *2-*8, *17, ABCB1 C3435T, PON1 Q192R and PON1 L55M. Minor allele frequency (MAF) was calculated. Patients were classified as one of the 5 categories by clopidogrel metabolizer phenotypes as extensive [without any "loss-of-function" (LOF) allele *2-*8 or "gain-of-function" (GOF) allele *17], intermediate (with only one LOF allele), Poor (with two or more LOF alleles), ultra (with one or two GOF alleles) or unknown (with one LOF allele and one GOF allele).</p><p><b>RESULTS</b>A total of 2800 ACS patients were enrolled [mean age (59.0 ± 12.3) years and 2236 males (79.9%)]. There were 74% patients with ST-segment elevation myocardial infarction (STEMI, n = 2072), 22.0% patients with non-ST-segment elevation myocardial infarction (NSTEMI, n = 617) and 4.0% patients with unstable angina (UA, n = 111). The minor allele frequency (MAF) for each genotype of CYP2C19 *2, *3, *4, *17 was 28.7%, 4.6%, 0.1% and 1.2%, respectively. There was no LOF allele *5-*8 in the study population. The MAF for ABCB1 C3435T, PON1 Q192R and PON1 L55M was 39.4%, 37.8% and 4.4%, respectively. Clopidogrel metabolizer groups were defined as extensive in 41.7%, intermediate in 45.6%, poor in 10.3%, ultra in 1.9% and unknown in 0.6% patients, respectively. There were no significant differences for all genotypes between males and females. Total LOF carriers of CYP2C19 were 56.4% and GOF carriers were 2.5%.</p><p><b>CONCLUSIONS</b>Our study demonstrated a high distribution of the LOF allele of CYP2C19 in China ACS population.</p>