Balkan Journal of Medical Genetics

CO-EXISTENCE OF CYP2C19*1/*2 AND ABCB1C.3435 CT GENOTYPE HAS A POTENTIAL IMPACT ON CLINICAL OUTCOME IN CAD PATIENTS TREATED WITH CLOPIDOGREL
Nestorovska KA, Naumovska Z, Staninova Stojovska M, Sterjev Z, Dimovski A, Suturkova Lj
*Corresponding Author: Aleksandra Kapedanovska Nestorovska, PhD, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Skopje, RN Macedonia, Mother Theresa str 47, 1000 Skopje, R. North Macedonia, Email address: alka@ff.ukim.edu.mk
page: 35

RESULTS

By comparison of the results obtained from the geno- typing and clinical presentation of the disease we observed that a negative clinical outcome is more frequent in the subgroup of patients treated with clopidogrel that carry the CYP2C19 *1/*2 genotype together with the ABCB1 CT genotype. These results indicate that those patients are at an increased risk of adverse cardiovascular events vs patients who are homozygotes for the normal allele (22.73% vs 9.62%; OR 3.455; 95% CI= [0.936-12.743], p=0.05722 (Table 2). Consequently, allelic distribution of the reduced-function allele, in the CYP2C19 and ABCB1 genes, was higher in patients with worse cardiovascular outcome (36.36% vs 21.15%) (Table 3, Figure1). Addi- tionally, in the subgroup of patients presented with the CYP2C19*1/*1 genotype and co-existence of the ABCB1 CC or CT genotype, we noted a trend towards higher risk of MACE occurrence compared to patients with the TT genotype (OR=1.316 TT→CT; OR=3.056 TT→CC). Based on the results from the CYP2C19/ABCB1 gen- otyping, patents were divided into three groups according to combined genotype/phenotype: extensive metabolizers (EM), intermediate metabolizers (IM) and poor metabolizers (PM) (Table 4). Patients carrying normal function alleles were classified as extensive metabolizers, patients carrying at least one or two loss-of-function allele were classified as intermediate metabolizers, whereas the pa- tients carrying two loss-of-function alleles were classified as poor metabolizers. In the subgroup of patients with neg- ative outcome, the presence of intermediate metabolizers was more frequent compared to the subgroup of patients with positive outcome (0.7272 vs 0.5192; p=0.02805). The frequency of patients referred to as poor metabolizers was higher in the subgroup with a positive outcome (0.2272 vs 0.3077; p=0.22842), but without statistical significance (Table 4). Therefore, the patients classified as intermediate metabolizers, carrying at least one loss-of-function allele were assumed to have higher risk of adverse cardiovascular events or MACE.

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