The Influence of Structural Variants of the Gene on the Pharmacokinetics of Enalapril, Presumably Due to Linkage Disequilibrium with the Intronic rs2244613.

Variants in the gene encoding carboxylesterase 1 may affect the metabolism of enalapril to the active metabolite enalaprilat. It was shown that the A allele of rs71647871 and the C allele of rs2244613 led to a decrease in plasma enalaprilat concentrations. This study aimed to estimate the effect of structural haplotypes of containing the pseudogene or a hybrid of the gene and the pseudogene on the pharmacokinetics of enalapril. We included 286 Caucasian patients with arterial hypertension treated with enalapril. Genotyping was performed using real-time PCR and long-range PCR. Peak and trough plasma enalaprilat concentrations were lower in carriers of . The studied haplotypes were in linkage disequilibrium with rs2244613: generally, the A allele was in the haplotype containing the , and the C allele was in the haplotype with the . Thus, carriers of have reduced CES1 activity against enalapril. Linkage disequilibrium of the haplotype containing the or with rs2244613 should be taken into account when genotyping the gene.