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Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an important marker of cardiovascular risk and a new target for therapeutic interventions. We aimed to study the influence of metformin on the level of circulating PCSK9 in patients with stable coronary artery disease (SCAD) and type 2 diabetes (T2DM) or metabolic syndrome (MetS), receiving moderate doses of statins used in routine clinical practice. Material and methods The study included 80 patients with T2DM or MetS receiving rosuvastatin for at least three months prior the study. MetS was diagnosed based on the Global Consensus Definition of the International Diabetes Federation (IDF). Serum level of PCSK9 was measured with an ELISA kit. Results Patients with T2DM or MetS, who took part in the research, were divided into 2 groups – those who received metformin prior the main study (21 patients – 1 st group) and patients who did not (59 patients – 2 nd group). Addition of metformin to the 3-month statin therapy of the 2nd group patients, divided into subgroup A ( n = 27) with the addition of metformin and subgroup B ( n = 29) without one, did not significantly affect the level of lipids. However, the level of circulating PCSK9 in subgroup A patients decreased, compared to subgroup B ( p < 0.01). At the same time, ongoing metformin and rosuvastatin therapy in the 1 st group patients was not accompanied by a further decrease of the PCSK9 level. Conclusions The addition of metformin to ongoing rosuvastatin therapy did not significantly affect serum lipid levels, but stabilized the level of circulating PCSK9, compared with the group without metformin treatment.

IntroductionThe objective is to study the influence of CYP3A5 (6986A>G), CYP2C9 (430C>T), CYP2C9 (1075A>C), SLCO1B1 (521T>C) and BCRP (ABCG2, 421C>A) gene polymorphisms on the development of simvastatin intolerance in ethnic Uzbek patients with coronary artery disease (CAD).Material and methodsThe case group contained 50 patients with clinical simvastatin-induced intolerance symptoms; the control group contained 50 patients without side-effects. Genotyping was performed by means of the PCR-RFLP method.ResultsAmong 37 patients with simvastatin-induced liver symptoms the *3/*3 genotype of the CYP3A5 gene (p = 0.0001) and variant genotype of the CA BCRP gene were observed more frequently than in the control group (p = 0.0001). However, when the 13 patients who had statin-associated muscle symptoms (SAMS) were compared with the control group (n = 50), it was found that in the case group the 3*/3* genotype of the CYP3A5 gene (OR = 8.6; 95% CI: 2.1–34.1; p = 0.003) and C allele carriers of the gene polymorphism SLCO1B1 (OR = 3.54; 95% CI: 1.35–9.27; Χ2 = 5.7; p = 0.017) were predominant.ConclusionsThe *3/*3 genotype of the CYP3A5 (6986A>G) gene and CA genotype of the BCRP (ABCG2, 421C>A) gene were associated with simvastatin-induced liver symptoms in ethnic Uzbek CAD patients, whereas in patients with simvastatin-associated muscle symptoms (SAMS), the combination of *3/*3 genotype of CYP3A5 (6986A> G) and carriage of the C allele of the SLCO1B1 gene polymorphism was predominant.

The aim of the research. To study the possible influence of polymorphism of the genes CYP3A5 (6986A> G), CYP2C9 (430C> T), CYP2C9 (1075A> C), SLCO1B1 (521T> C) and BCRP (ABCG2, 421C> A) on the occurrence of muscle symptoms in the treatment of simvastatin in patients with coronary heart disease, ethnic Uzbeks. Material and methods. In the "case-control" study, 63 patients with chronic coronary heart disease (CHD) were included. The "case" group was consisted of 13 patients who had clinical signs of myopathy, and 4 of them simultaneously showed an increase in the level of transaminases > 3 times. The "control" group included 50 patients with chronic coronary heart disease, without side effects when treated with simvastatin. Genotyping was performed by the PCR-RFLP method. Results. When comparing the prevalence of the most common homozygous genotypes with variant, it turned out that the genotype * 3 / * 3 of the CYP3A5 gene was prevailed in the "case" group (OSh 8.56, 95% DI 2.14-34.1, P = 0.003). When comparing the distribution frequency of alleles the SLCO1B1 gene in the group "case" the carriage of allele C was prevailed (OSh 3.54, 95%, DI 1.35-9.27, χ² = 5.7, P = 0.017). Conclusion. In patients with CHD, ethnic Uzbeks, the carriage of the genotype *3/*3 of the CYP3A5 gene and the C allele of SLCO1B1 gene is associated with muscular symptoms caused by simvastatin.

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