title: Functional gene polymorphism of matrix metalloproteinase-1 is associated with benign hyperplasia of myo- and endometrium in the Russian population.
abstract: OBJECTIVE
  Estrogen-dependent hyperplasia of myo- and endometrium manifests as uterine leiomyoma or adenomyosis. We studied possible associations between common polymorphisms of matrix metalloproteinase (MMP) genes and clinical features of uterine hyperplasia.
  
  
  METHODS
  One hundred seventy female patients with uterine leiomyoma (46.6±0.5 years) were observed. Clinical diagnosis was based on physical examination, ultrasonography, and histological data. MMP-1 (-1607 1G/2G, rs1799750) and MMP-3 (-1171 5A/6A, rs3025058) were genotyped with allele-specific polymerase chain reaction (PCR) of leukocyte DNA. Clinical and genetic data were evaluated using nonparametric statistics.
  
  
  RESULTS
  Distributions of MMP-1 and MMP-3 promoter alleles among patients and population controls were similar and corresponded to the Hardy-Weinberg equilibrium (HWE). Detectable tumor growth and adenomyosis were observed, respectively, in 71% and 55% of cases. Steady-state leiomyoma correlated with a higher prevalence of the MMP-1 1G/1G genotype (p=0.02 by χ(2) test). Accelerated tumor growth correlated with higher frequency of the MMP-1 2G allele [odds ratio (OR)=2.048, p=0.039, χ(2)=4.2611, confidence interval (CI)=(1.032-4.062)]. MMP-1 2G was also associated with multinodular growth [OR=3.561, p=0.01249, χ(2)=6.24, CI=(1.261-10.058)]. The MMP-1 2G allele tended to increase in patients with adenomyosis [OR=1.525, p=0.054, χ(2)=3.71, CI=(0.992-2.345)].
  
  
  CONCLUSIONS
  Our pilot study suggests that the 2G (-1607)MMP-1 genotype may be a potential risk marker of myo- and endometrial hyperplasia.
authors.affiliation: Research Center for Molecular Medicine, St. Petersburg State Medical I.P. Pavlov University, St. Petersburg, Russia.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Morosova
authors.forename: Alexei B
authors.initials: AB
authors.lastname: Chukhlovin
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Kulagina
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Kipich
authors.forename: Areg A
authors.initials: AA
authors.lastname: Totolian
mesh_terms: D062788:Adenomyosis / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000483:Alleles; D004717:Endometrium / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007889:Leiomyoma / Q000235:genetics* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012426:Russia; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology; D044465:White People / Q000235:genetics*
chemical_list: D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1