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The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
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Obstetrics and Gynegology2024№10
Association between xenobiotic detoxification system...

Association between xenobiotic detoxification system gene polymorphisms and hormone replacement therapy efficacy in women with premature ovarian insufficiency

DOI
https://dx.doi.org/10.18565/aig.2024.243

Averkova V.G., Donnikov A.E., Yureneva S.V.

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia

Objective: To evaluate the association between xenobiotic detoxification system gene polymorphisms and hormone replacement therapy (HRT) efficacy in patients with premature ovarian insufficiency (POI).
Materials and methods: This study included 83 women with POI who exhibited persistent symptoms of estrogen deficiency while receiving HRT E2/DYD 2 mg/10 mg. The participants were divided into two groups: group 1 (n=23) included patients with signs of severe estrogen deficiency (GCS score > 20 and E2 blood level <150 pmol/l) and group 2 (n=60) included those with a GCS score < 20 and an E2 blood level >150 pmol/l. Genotyping was performed by real-time PCR. The distribution frequencies of alleles and genotypes for the polymorphisms were analyzed in both groups. The χ² test assessed the significance of the differences (p). The strength of the association between features was evaluated using the odds ratio (OR).
Results: Allele A of the A313G polymorphism of GSTP1 and allele C of the C341T polymorphism of GSTP1 were associated with severe estrogen deficiency in patients receiving HRT E2/DYD 2 mg/10 mg (OR=2.99, 95% CI 1.07–8.33, p=0.03; OR=7.43, 95% CI 0.96–57.52, p=0.03). The AC haplotype (risk haplotype) for the GSTP1 A313G (Ile105Val) and GSTP1 C341T (Ala114Val) polymorphisms was significantly more frequently detected in patients with severe estrogen deficiency during HRT (69.6% in group 1 versus 43.3% in group 2, p=0.049, OR=2.99, 95% CI 0.97–9.80). The -341 C/C genotype was identified as a marker of the risk haplotype based on haplotype and individual genotype correspondence assessment.
Conclusion: GSTP1 gene polymorphisms play a significant role in the response to HRT in patients with POI, likely due to their influence on the regulation of E2 detoxification processes.

Authors' contributions: Averkova V.G. – obtaining data for analysis, material processing and analyzing, statistical analysis, drafting of the manuscript; Donnikov A.E. – editing of the manuscript; Yureneva S.V. – conception and design of the study, editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: There was no funding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P (Ref. No: 1 of 07 February 2019).
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Averkova V.G., Donnikov A.E., Yureneva S.V. Association between xenobiotic detoxification system gene polymorphisms and hormone replacement therapy efficacy in women with premature ovarian insufficiency.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (10): 113-120 (in Russian)
https://dx.doi.org/10.18565/aig.2024.243

Keywords

premature ovarian insufficiency
hormone replacement therapy
estrogen deficiency
gene variants
single nucleotide polymorphism
Full text (in Russian)

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Received 07.10.2024

Accepted 17.10.2024

About the Authors

Victoria G. Averkova, Researcher, Institute of Oncology and Mammology, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, buch1202@mail.ru, https://orcid.org/0000-0002-8584-5517
Svetlana V. Yureneva, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology of the Department of Vocational Education, Deputy Director for Science, Institute of Oncology and Mammology, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, syureneva@gmail.com,
https://orcid.org/0000-0003-2864-066X
Andrey E. Donnikov, PhD, Head of the Laboratory of Molecular Genetic Methods, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Oparin str., 4, donnikov@dna-technology.ru, https://orcid.org/0000-0003-3504-2406
Corresponding author: Victoria G. Averkova, buch1202@mail.ru

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