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

Elena B Morosova, Morosova EB, Elena Morosova, Alexei B. Chukhlovin, Chukhlovin AB, Kulagina NV, Natalia V Kulagina, Kipich NV, Natalia V Kipich, Areg A Totolian, Арег А. Тотолян
Genetic testing and molecular biomarkers · 2012 · vol. 16(9) , pp. 1032–1037 · doi:10.1089/gtmb.2011.0376 · PMID:22853432 · PMC3438823 · W2045863767
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The 2G allele of the MMP-1 gene polymorphism was associated with accelerated tumor growth, multinodular growth, and a tendency towards adenomyosis in Russian women with benign uterine hyperplasia.

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Abstract

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.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Leiomyoma Matrix Metalloproteinase 1 Polymorphism, Genetic Uterine Neoplasms White People Adenomyosis Adenomyosis Adult Alleles Endometrium Endometrium Female Gene Frequency Genotype Humans Hyperplasia Hyperplasia Hyperplasia Leiomyoma

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