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Catechol-O-methyltransferase Val158Met polymorphism is associated with increased risk of multiple uterine leiomyomas either positive or negative for MED12 exon 2 mutations
  1. Lyailya Kh Dzhemlikhanova1,2,
  2. Olga A Efimova1,2,
  3. Natalia S Osinovskaya1,
  4. Sergey E Parfenyev2,
  5. Dariko A Niauri1,2,
  6. Iskender Yu Sultanov1,
  7. Olga V Malysheva1,
  8. Anna A Pendina1,2,
  9. Natalia Yu Shved1,
  10. Tatyana E Ivashchenko1,
  11. Maria I Yarmolinskaya1,
  12. Maka I Kakhiani1,
  13. Ekaterina A Gorovaya2,
  14. Antonina N Tkachenko3,
  15. Vladislav S Baranov1,2
  1. 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia
  2. 2St. Petersburg State University, St. Petersburg, Russia
  3. 3Maternity Hospital of St. Petersburg №6, St. Petersburg, Russia
  1. Correspondence to Dr Olga A Efimova, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya line, 3, St. Petersburg 199034, Russia; efimova_o82{at}


Aims To study the possible association of catechol-O-methyltransferase (COMT) Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to check whether the COMT Val/Val genotype is associated with MED12 exon 2 mutations in fibroids.

Methods The COMT Val158Met allele and genotype frequencies were compared between age-matched women with ULs (n=104) and controls (n=59). Patients with UL were subcategorised by diagnosis of solitary (n=59) or multiple (n=45) fibroids and by the presence of somatic MED12 exon 2 mutations in at least one fibroid (n=32) or in neither fibroid (n=26). The association of COMT Val/Val genotype with the presence of any ULs, solitary/multiple ULs and ULs positive/negative for MED12 exon 2 mutations was evaluated by χ2 tests using a dominant genotype model (G/G vs G/A+A/A) and expressed as ORs and 95% CIs.

Results The COMT Val/Val genotype frequency did not differ between the patients with UL and the controls (28.8% vs 18.6%, p=0.149, OR 1.77; CI 0.81 to 3.86). However, it was significantly higher in the patients who had multiple UL compared with the solitary UL (40% vs 20.3%, p=0.028, OR 2.61; CI 1.09 to 6.24) and to the controls (40% vs 18.6%, p=0.016, OR 2.91; CI 1.20 to 7.06). No association of the COMT Val/Val genotype with UL-specific MED12 exon 2 mutations was found (p=0.662, OR 0.77; CI 0.23 to 2.53).

Conclusions Women with COMT Val/Val genotype are at high risk of developing multiple uterine fibroids either positive or negative for MED12 exon 2 mutations. These data are important to design new strategies for UL prophylaxis and treatment.


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  • Handling editor Runjan Chetty

  • Contributors Study design: LKD, OAE, AAP, DAN, TEI, VSB; recruitment of patients and controls, sampling, processing of medical history data: LKD, DAN, NYS, MIY, MIK; COMT Val158Met polymorphism analysis: LKD, NSO, IYS, EAG, ANT; MED12 exon 2 mutation analysis: NSO, IYS, OVM, NYS; statistical analysis: OAE, SEP; data interpretation: LKD, OAE, NSO, SEP, DAN, OVM, AAP, TEI, EAG, ANT; literature search and manuscript drafting: OAE; critical revision of the manuscript for important intellectual content: TEI, MIY, MIK, VSB.

  • Funding The study of the COMT Val158Met polymorphism association with UL risk was performed as a part of research project ‘Molecular mechanisms of the development of benign synchronic and polymethachronic pathological proliferations in female reproductive system at the organ and tissue level’ (project no, St. Petersburg State University). The part of this study concerning the detection of MED12 exon 2 mutations in ULs was supported by the Russian Scientific Foundation (project no 14-15-00737). OAE is a grantee of RF President Scholarship (SP—1405.2015.4).

  • Competing interests None declared.

  • Ethics approval Ethics Committee of D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology.

  • Provenance and peer review Not commissioned; externally peer reviewed.