title: Catechol-O-methyltransferase Val158Met polymorphism is associated with increased risk of multiple uterine leiomyomas either positive or negative forMED12exon 2 mutations.
abstract: OBJECTIVE
  To study the possible association of catechol-O-methyltransferase (COMT)Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to check whether theCOMTVal/Val genotype is associated withMED12exon 2 mutations in fibroids.
  
  
  METHODS
  TheCOMTVal158Met 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 somaticMED12exon 2 mutations in at least one fibroid (n=32) or in neither fibroid (n=26). The association ofCOMTVal/Val genotype with the presence of any ULs, solitary/multiple ULs and ULs positive/negative forMED12exon 2 mutations was evaluated by χ2tests using a dominant genotype model (G/G vs G/A+A/A) and expressed as ORs and 95% CIs.
  
  
  RESULTS
  TheCOMTVal/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 theCOMTVal/Val genotype with UL-specificMED12exon 2 mutations was found (p=0.662, OR 0.77; CI 0.23 to 2.53).
  
  
  CONCLUSIONS
  Women withCOMTVal/Val genotype are at high risk of developing multiple uterine fibroids either positive or negative forMED12exon 2 mutations. These data are important to design new strategies for UL prophylaxis and treatment.
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.|St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Lyailya Kh
authors.initials: LK
authors.lastname: Dzhemlikhanova
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.|St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Olga A
authors.identifier: http://orcid.org/0000-0003-4495-0983
authors.initials: OA
authors.lastname: Efimova
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Osinovskaya
authors.affiliation: St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Parfenyev
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.|St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Dariko A
authors.initials: DA
authors.lastname: Niauri
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.
authors.forename: Iskender Yu
authors.initials: IY
authors.lastname: Sultanov
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Malysheva
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.|St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Pendina
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.
authors.forename: Natalia Yu
authors.initials: NY
authors.lastname: Shved
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.
authors.forename: Tatyana E
authors.initials: TE
authors.lastname: Ivashchenko
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Yarmolinskaya
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.
authors.forename: Maka I
authors.initials: MI
authors.lastname: Kakhiani
authors.affiliation: St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Gorovaya
authors.affiliation: Maternity Hospital of St. Petersburg №6, St. Petersburg, Russia.
authors.forename: Antonina N
authors.initials: AN
authors.lastname: Tkachenko
authors.affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia.|St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Vladislav S
authors.initials: VS
authors.lastname: Baranov
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007889:Leiomyoma / Q000235:genetics*; D056892:Mediator Complex / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D014594:Uterine Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: FERTILITY; GENETICS; HORMONE; UTERUS