Lipid-lowering efficacy of atorvastatin in patients with CYP3A4 gene allele mutation

Relevance. Pharmacogenetics is one of the leading areas of personalized medicine, allowing the prediction of the effectiveness and safety of medicines

in a particular patient. This study analyzed the presence of CYP3A4 gene allele mutations and their relationship with the effectiveness of therapy.

Objective. This study aimed to evaluate the effect of the genetic polymorphism A/G (rs2740574) of the CYP3A4 gene, as well as polymorphisms CYP3A4_2 Leu293Pro (rs28371759) and CYP3A4 Phe189Ser (rs4987161) in patients with coronary heart disease on the lipid-lowering efficacy of atorvastatin in real-world practice.

Materials and methods. This study included 96 patients with coronary artery disease who received atorvastatin therapy. Molecular genetic analysis of CYP3A4 gene polymorphisms was performed using real-time polymerase chain reaction. Statistical data processing was performed using STATA 14 software.

Results. The frequency of the G allele (rs2740574) in the studied sample was 8.3 %, which differed significantly from that of the all-Russian (4 %, p = 0.0095) and European (3.63 %, p = 0.0005) populations. The frequency of the minor C allele for the CYP3A4_2 Leu293Pro (rs28371759) polymorphism was 0.5%, which was significantly different from the global and European frequencies (p < 0.001). Polymorphism CYP3A4 Phe189Ser (rs4987161) was not detected in the sample. Carriers of the G allele (rs2740574) (n = 15) showed a significant decrease in total cholesterol (from 5.38 ± 1.49 to 3.23 ± 0.96 mmol/l, p = 0.0019) and LDL-C (from 3.54 ± 1.17 to 1.58 ± 0.62 mmol/l, p = 0.0004) during atorvastatin therapy. The effect of other polymorphisms on the lipid profile could not be assessed due to their low prevalence.

Conclusion. Unique frequencies of CYP3A4 gene alleles, which differ from the reference populations, have been identified in patients with coronary heart disease in Arkhangelsk. The presence of the G allele (rs2740574) is associated with a more pronounced lipid-lowering response to atorvastatin therapy. The findings highlight the importance of pharmacogenetic studies for the personalization of statin therapy.

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