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

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.

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.

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).

The data obtained suggest the participation of oxytocin and its receptor in the pathogenesis of adenomyosis and requires further research in this direction. Full Text About the authors Elena A. Netreba The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] 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: [email protected] ORCID iD: 0000-0002-6551-4147 SPIN-code: 3686-3605 MD, Dr. Sci. (Med.), Professor of the Russian Academy of Sciences Russian Federation, Saint PetersburgOlga V. Malysheva The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-8626-5071 SPIN-code: 1740-2691 Cand. Sci. (Biol.) Russian Federation, Saint PetersburgMaria A. Shalina The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-5921-3217 SPIN-code: 6673-2660 MD, Cand. Sci. (Med.) Russian Federation, Saint PetersburgNatalia N. Tkachenko The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0001-6189-3488 SPIN-code: 9633-6701 Cand. Sci. (Biol.) Russian Federation, Saint PetersburgAnastasia V. Koloshkina The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-5200-7672 Russian Federation, Saint Petersburg

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