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Influence of polymorphism of genes encoding products of lipid metabolism on the effectiveness of statins in patients with stable coronary artery disease

Authors: Koksheneva I.V., Temirbulatova T.R., Grishenok A.V.

Company: Bakoulev National Medical Research Center for Cardiovascular Surgery, Moscow, Russian Federation

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Type:  Original articles


DOI: https://doi.org/10.24022/1997-3187-2024-18-1-44-58

For citation: Koksheneva I.V., Temirbulatova T.R., Grishenok A.V. Influence of polymorphism of genes encoding products of lipid metabolism on the effectiveness of statins in patients with stable coronary artery disease. Creative Cardiology. 2024; 18 (1): 44–58 (in Russ.). DOI: 10.24022/1997-3187-2024-18-1-44-58

Received / Accepted:  10.01.2024 / 06.02.2024

Keywords: atherosclerosis lipid-lowering therapy effectiveness of statin therapy genetic variability genetic polymorphism of apolipoprotein E



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Abstract

Material and methods. The study included 84 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI). 23 single nucleotide polymorphisms (SNPs) of 12 candidate genes involved in the regulation of lipid metabolism were genotyped: ABCA1 (rs2740483; rs1800977; rs1800977), LPL (rs268; rs285; rs328; rs1801177; rs2083637; rs10096633 ), PCSK9 (rs505151). APOA5 (rs964184), APOC3 (rs2854116; rs4520; rs5128), APOE (rs405509; rs429358+rs7412), LPA (rs1853021), PON1 (rs854560; rs662), TRIB1 (rs29540029), LRP8 (rs5174 ), ANGPTL3 (rs10889353), XKR6-AMAC1L2 (rs7819412). A lipid profile study was carried out initially before the PCI procedure, 1 month, 3 months, 6 months, 1 year after PCI and at longterm follow-up visits. The distribution of genotypes and alleles of selected candidate genes was analyzed in two groups: group 1 – 52 patients who achieved target lipid levels while taking statins; group 2 – 32 patients who failed to achieve target lipid levels while taking statins.

Results. Associations of carriage of two SNPs were identified: APOE rs405509 (CC genotype) (odds ratio (OR) 2.05 95% CI 1.0–5.28; p=0.05) and APOE (rs429358+rs7412) allele ε4 (OR 3.47 95% CI 1.28–9.42; p=0.01) and genotypes ε3ε4+ε4ε4 (OR 3.58 95% CI 1.19–10.73; p=0.01) with insufficient effectiveness of therapy statins.

Conclusion. The study confirmed the contribution of genetic factors to the reduction in the effectiveness of statin therapy in patients with CAD. The results indicate that in addition to standard statin therapy, in patients with CAD who are carriers of the risk alleles – ε4 APOE (rs429358+rs7412) and genotype CC APOE rs405509, it is necessary to develop individual optimal lipid-lowering therapy regimens to reduce cardiovascular risk caused by genetically determined abnormal lipoprotein metabolism.

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About Authors

  • Inna V. Koksheneva, Dr. Med. Sci., Senior Researcher; ORCID
  • Tabarik R. Temirbulatova, Postgraduate
  • Alena V. Grishenok, Postgraduate

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


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