Functional gene polymorphism of matrix metalloproteinase-1 is associated with benign hyperplasia of myo- and endometrium in the Russian population.

AIMS: 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.

PATIENTS AND

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)].

CONCLUSION

Our pilot study suggests that the 2G (-1607)MMP-1 genotype may be a potential risk marker of myo- and endometrial hyperplasia.