Functional Gene Polymorphism of Matrix Metalloproteinase-1 Is Associated with Benign Hyperplasia of Myo-and Endometrium in the Russian Population

摘要

Aims: Estrogen-dependent hyperplasia of myo- and endometrium manifests as uterine leiomyoma or adeno-myosis. 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, ultra-sonography, and histological data. MMP-1 (-1607 1G/2G, rsl799750) 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.