Pharmacogenomics of anti-platelet therapy focused on peripheral blood cells of coronary arterial disease patients.

ABSTRACT

BACKGROUND: To investigate genes differentially expressed in peripheral blood cells (PBCs) from patients with coronary arterial disease (CAD) under double anti-platelet therapy. METHODS: Twenty-six CAD patients that were submitted to percutaneous coronary intervention (PCI) were selected to participate in this study. These patients took 100mg/day of acetylsalicylic acid (ASA) and 75mg/day of clopidogrel. Blood samples were collected before PCI to evaluate platelet reactivity using VerifyNow ASA and P2Y12 assays (Accumetrics). The patients were stratified into 4 quartiles based on ASA reaction units (ARUs) and P2Y12 reaction units (PRUs). Quartile 1 (Q1) patients were classified as responders and quartile 4 (Q4) patients as non-responders. Global mRNA expression from Q1 to Q4 was analyzed by microarray using the GeneChip Exon 1.0 ST array (Affymetrix) and was confirmed by RT-qPCR. RESULTS: Patients with ARU or PRU values within the first quartile (Q1, ARU<390 and PRU<151) were considered responders, while those who had ARU or PRU within the fourth quartile (Q4, ARU>467 and PRU>260) were considered nonresponders. The risk factors associated for CAD showed expected frequencies and no difference was found between Q1 and Q4. Microarray analysis identified 117 genes differentially expressed for ASA and 29 for clopidogrel between Q1 and Q4 groups (p<0.01, FC>1.2). CONCLUSION: The variation in response to ASA may be related with an increased expression of IGF1 and IGF1R, as well as a response to clopidogrel can be affected by pharmacokinetic change related to the reverse transport pathway by increased expression of ABCC3.