PB1390 - Pharmacogenetic analysis and novel coronavirus infection – perspectives of real clinical practice

Background: In light of the COVID-19 pandemic, personalized medicine has become especially relevant. Pharmacogenetics is an important element of this area, taking into account the genetic characteristics of the patient.

Aims: To analyze the prevalence of genetic polymorphism of the cytochrome P-450 system in patients with COVID-19.

Methods: A prospective clinical and laboratory study was performed during the COVID-19 pandemic (December 2020 - March 2021) on the basis of the Regional Center for Antithrombotic Therapy "First City Clinical Hospital” (Arkhangelsk) with the inclusion of 63 patients with a severe course of a new coronavirus infection. The study design was approved by the local ethics committee (protocol No. 2/20 April 23, 2020). A sample of genomic DNA obtained from peripheral blood leukocytes was used as the material for the study. Determination of the sequence of polymorphism of the genes of the biotransformation system CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910) and CYP3A4*1A/1B (rs2740574) was performed by polymerase chain reaction (PCR) DNA synthesis in the "real time" mode on a Real-Time CFX96 amplifier . Statistical calculations were carried out using the STATA 14 program, the Hardy-Weinberg test and Pearson's chi-square.

Results: In the examined patients, the most common heterozygous genotypes of the CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) genes (76.19% and 77.78%, respectively) and the wild homozygous CYP3A4*1A/1B genotype (rs2740574) (71 .43%). An unfavorable interaction of the heterozygous genotype and mutant homozygous polymorphism of the CYP2C9*3 gene (rs1057910) with the intake of nadroparin calcium (x2=3.3642, p=0.067 and x2=3.3642, p=0.067), as well as with the simultaneous intake of nadroparin calcium was revealed. and favipiravir (x2=4.8395, p=0.028 and x2=4.8395, p=0.028).

Conclusion(s): The results of the study indicate the importance of an individual approach to the choice of pharmacotherapy for COVID-19 infection and the feasibility of further research in the field of pharmacogenetics of this infection.