engleski

CYP2C9 and ABCG2 polymorphisms as risk factors for developing adverse drug reactions in renal transplant patients taking fluvastatin: a case- control study

Aim was to investigate whether an association exists between fluvastatin-induced adverse drug reactions (ADRs) and polymorphisms in genes encoding the metabolizing enzyme CYP2C9 and the drug transporter ABCG2 in renal transplant recipients (RTRs). Fifty-two RTRs that experienced fluvastatin ADRs and 52 controls matched for age, gender, dose of fluvastatin and immunosuppressive use were enrolled in the study. Genotyping for CYP2C9*2, *3 and ABCG2 421C>A variants was performed by real- time PCR. RESULTS: CYP2C9 homozygous and heterozygous mutant allele (*2 or *3) carriers had 2.5-times greater odds of developing adverse effects (χ² = 4.370 ; degrees of freedom = 1 ; p = 0.037 ; φ = 0.21, odds ratio [OR]: 2.44 ; 95% CI: 1.05-5.71). Patients who were the carriers of at least one mutant CYP2C9 allele (*2 or *3) and who were receiving CYP2C9 inhibitors, had more than six-times greater odds of having adverse effects than those without the inhibitor included in their therapy (p = 0.027 ; OR: 6.59 ; 95% CI: 1.24-35.08). Patients with ABCG2 421CA or AA (taken together) had almost four-times greater odds of developing adverse effects than those with ABCG2 421CC genotype (χ² = 6.190 ; degrees of freedom = 1 ; p = 0.013 ; φ = 0.24, OR: 3.81 ; 95% CI: 1.27-11.45). Patients with A allele had 2.75- times (95% CI: 1.02-7.40) greater odds of developing adverse effects than those with C allele. Our preliminary data demonstrate an association between fluvastatin-induced ADRs in RTRs and genetic variants in the CYP2C9 and ABCG2 genes.

adverse drug reactions; CYP2C9; ABCG2; drug interactions; fluvastatin; hydroxymethylglutaryl-CoA reductase inhibitors; pharmacogenetics

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