Архивъ внутренней медицины (Feb 2018)

PHARMACOGENETIC FEATURES OF THERAPY OF PATIENTS WITH ATHEROSCLEROSIS

  • A. L. Khokhlov,
  • A. N. Yavorsky,
  • N. O. Pozdnyakov,
  • J. V. Rybachkova,
  • E. S. Emelianov,
  • A. A. Khokhlov,
  • A. E. Miroshnikov,
  • S. O. Pozdnyakov

DOI
https://doi.org/10.20514/2226-6704-2018-8-1-45-52
Journal volume & issue
Vol. 8, no. 1
pp. 45 – 52

Abstract

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The complexity of therapy of lipid metabolism disorders is not only in comorbidity and polypragmasia, but also in predicting a genetically determined response to the treatment. The aim of our work was to study the pharmacogenetics features of pharmacotherapy of patients with non-alcoholic fatty liver disease, with various forms of IHD, and patients taking statins. We investigated 4 study groups: I — 60 patients with 2 type of diabetes and non-alcoholic fatty liver disease (APOE polymorphism); II — 187 patients with IHD (eNOS, AGTR2, CYP2D6 polymorphisms); III — 111 people with AH and CHF (polymorphisms: AGT: 704 (Met235Thr), AGT:521 (Thr174Met), AGTR1: 1166, AGTR2: 1675, CYP11B2: -344, GNB3: 825, ADD1: 1378 (Gly460Trp), NOS3: -786); IV — 62 patients taking atorvastatin (SLCO1B1*5 polymorphism). Patients with E2, E4 alleles of the APOE gene, taking essential phospholipids, improved parameters of total cholesterol, HDL, LDL, CA, AP; patients with E3 alleles had a positive dynamics of cholesterol, HDL, TG, LDL, VLDL, CA, urea. Patients having “slow” allelic variants of the gene CYP2D6*10, CYP2D6*4 had received metoprolol, had greater decrease in heart rate: 1.6 times for CYP2D6*10, 1.7 — for CYP2D6*4. Earlier debut of IHD is noted in patients with TT variants of the eNOS gene comparing the patients with GG and GT variants. Dosages of perindopril depend on AGTR2 gene polymorphisms. The prevalence of polymorphisms AGTR2: 1675, CYP11B2: -344, NOS3: -786, AGT: 704, GNB3: 825 increases with the increase in the stage of CHF. The parameters of intracardiac hemodynamics in patients with CHF are associated with AGT: 704, NOS3:-786, GNB3: 825, ADD1: 1378, AGT: 521 polymorphisms. Allele C of the SLCO1B1*5 gene is associated with an additional risk of statin-induced myopathy. So the treatment of diseases associated with atherosclerosis, needs using of a personalized approach for more effective and safe therapy.

Keywords