Фармация и фармакология (Пятигорск) (Jul 2025)

Prevalence of AOX1 and CYP1A2 gene polymorphisms associated with response to favipiravir therapy in novel coronavirus infection COVID-19 among ethnic groups of the North Caucasus

  • A. T. Leinsoo,
  • N. P. Denisenko,
  • Sh. P. Abdullaev,
  • S. N. Tuchkova,
  • A. V. Kryukov,
  • S. N. Mammaev,
  • Zh. A. Sozaeva,
  • M. S.-Kh. Sozaeva,
  • K. A. Akmalova,
  • L. Z. Bolieva,
  • A. I. Dobroselskaya,
  • M. L. Maksimov,
  • K. B. Mirzaev,
  • D. A. Sychev

DOI
https://doi.org/10.19163/2307-9266-2024-12-6-420-430
Journal volume & issue
Vol. 12, no. 6
pp. 420 – 430

Abstract

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Drug sensitivity to, in particular to favipiravir, may vary among representatives of different ethnic groups. Studies have previously shown that carrying certain variants of the AOX1 and CYP1A2 genes may be associated with an increased incidence of adverse reactions with patients having COVID-19 and taking favipiravir. This work is devoted to studying the prevalence of mutant variants rs55754655 and rs10931910 of the AOX1 gene and rs762551 of the CYP1A2 gene in various ethnic groups of the North Caucasus.The aim. To characterize the distribution structure of AOX1 (rs55754655 and rs10931910) and CYP1A2 (rs762551) variants among the peoples of the North Caucasus (Ossetians, Balkars, Kabardians, Avars, Dargins, Laks, Kumyks and Lezgins).Materials and methods. The frequency of distribution of AOX1 and CYP1A2 gene variants was studied among 897 conditionally healthy volunteers (362 men — 40.4% and 535 women — 59.6%; average age — 34.6±6.3%), from 8 ethnic groups of the North Caucasus: Ossetians, Balkars, Kabardians, Avars, Dargins, Laks, Kumyks and Lezgins (n=100 for each), as well as 97 Russians (reference group).Results. As a result of the analysis, a significant difference was found in the allele frequencies for the rs10931910 AOX1 genetic polymorphism between Balkars and Russians (p <0.05), Laks and Russians (p <0.05), and especially between Dargins and Russians (p <0.0001). No statistically significant differences in the allele frequencies of the CYP1A2 gene were found in the comparative analysis of ethnic groups with the comparison group.Conclusion. Significant differences were revealed in the frequency of AOX1 polymorphisms (rs10931910, rs55754655) in the peoples of the North Caucasus relative to the Russian population. The largest deviations were recorded in Dargins: a decrease in the frequency of the minor allele rs10931910 to 28.5% (p <0.0001) and rs55754655 to 3.0% (p=0.0105). The results may be useful for optimizing therapy with medicines that are AOX1 substrates, which include favipiravir, used to treat patients with COVID-19.

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