Connection of the Genetic Polymorphism Cyp3a5 and Slco1b1 With the Muscular Symptoms, Caused by Simvastatin in Patients With Chd, Ethnic Uzbeks: Results of the Case-Control Study

Abstract

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.

Candidate Genes for Prediction of Efficacy and Safety of Statin Therapy in the Kazakh Population

“…In the same study conducted by Uzbek scientists (Shek et al, 2017), the group of patients with coronary artery disease and good statin tolerance had the frequency of the C allele of the 521T>C mutation equal to 0.150. The group of patients who had side effects and complications after the use of statins, the frequency of this allele was 0.385 (χ² = 5.7; p = .017).…”

“…In a study conducted in the Uzbek population, the frequency of the GG genotype in the group of patients with cardiovascular diseases and good statin tolerance was 0.120, while that in the group with clinical signs of complications was – 0.538 (χ 2 = 8.63; p = .003) (Shek et al, 2017). If comparing these results with the cited ones (the frequency of the GG genotype is 0.112), there is no considerable difference in the frequency of the mutant homozygous genotype between the two populations.…”