Blood oxytocin levels and the rs4686302 polymorphism of the oxytocin receptor gene in patients with adenomyosis

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Abstract

BACKGROUND: An in-depth study of the pathogenesis of adenomyosis and the development of new therapeutic approaches are extremely relevant. Atosiban, a competitive oxytocin receptor antagonist, may be a promising drug with a potential therapeutic effect. Oxytocin is involved in the pathogenesis of adenomyosis-associated dysmenorrhea, and there is evidence of increased expression of the oxytocin receptor (OXTR) in the myometrium in adenomyosis and the association of the OXTR gene polymorphic variant rs4686302 with oxytocin-induced myometrial contractility.

AIM: The aim of this study was to evaluate blood oxytocin levels and the frequency of the polymorphic variants of the oxytocin receptor gene (OXTR) rs4686302 polymorphism in patients with adenomyosis and in healthy women of reproductive age.

MATERIALS AND METHODS: The levels of oxytocin in the blood plasma were measured by competitive enzyme immunoassay (ELISA) in patients with adenomyosis (n = 56, with mean age of 37.5 ± 8.54 years), and in women without gynecological diseases (control group; n = 33, with mean age of 32.1 ± 5.40 years). The polymorphic variant rs4686302 of the OXTR gene was analyzed by PCR-RFLP analysis in patients with adenomyosis (n = 79, with mean age of 39.9 ± 7.74 years) and in control group patients (n = 49, with mean age of 37.0 ± 9.20 years). The chi-square (χ2) test was used to analyze the distribution of genotypes and alleles. Statistical data processing was performed using the Jamovi Software, Version 1.2.27 for Windows.

RESULTS: In patients with adenomyosis, the level of oxytocin in the blood serum was significantly higher than in control group patients: 130.0 ± 27.9 pg/ml and 95.9 ± 26.7 pg/ml, respectively. The minor allele A of the OXTR gene polymorphic variant rs4686302 was significantly more common in patients with adenomyosis (28.5%) than in women in the control group (13.3%) and in the general sample (11–15% according to the 1000 Genomes Project). The odds of developing adenomyosis in patients with the presence of the A allele (the G/A and A/A genotypes) were 2.44 times higher compared to patients with the G/G genotype (OR 2.44, 95% CI 1.13–5.28).

CONCLUSIONS: The data obtained suggest the participation of oxytocin and its receptor in the pathogenesis of adenomyosis and requires further research in this direction.

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About the authors

Elena A. Netreba

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: dr.netlenka@yandex.ru
ORCID iD: 0000-0002-0485-3612
SPIN-code: 9193-3154
Russian Federation, Saint Petersburg

Maria I. Yarmolinskaya

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605

MD, Dr. Sci. (Med.), Professor of the Russian Academy of Sciences

Russian Federation, Saint Petersburg

Olga V. Malysheva

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: omal99@mail.ru
ORCID iD: 0000-0002-8626-5071
SPIN-code: 1740-2691

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Maria A. Shalina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: amarus@inbox.ru
ORCID iD: 0000-0002-5921-3217
SPIN-code: 6673-2660

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Natalia N. Tkachenko

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: liberin@mail.ru
ORCID iD: 0000-0001-6189-3488
SPIN-code: 9633-6701

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Anastasia V. Koloshkina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: nastyasalukhova@gmail.com
ORCID iD: 0000-0002-5200-7672
Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Visualization of genomic DNA research by cutting DNA using restriction endonuclease enzymes and further analysis of the resulting fragment sizes using gel electrophoresis

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3. Fig. 2. Oxytocin blood levels in patients of the study groups

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4. Fig. 3. Mean oxytocin blood levels in patients with adenomyosis with the G/G and G/A genotypes of the oxytocin receptor gene (OXTR) polymorphic variant rs4686302

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