Morosova Elena B, Chukhlovin Alexei B, Kulagina Natalia V, Kipich Natalia V, Totolian Areg A
Research Center for Molecular Medicine, St. Petersburg State Medical I.P. Pavlov University, St. Petersburg, Russia.
Genet Test Mol Biomarkers. 2012 Sep;16(9):1032-7. doi: 10.1089/gtmb.2011.0376. Epub 2012 Aug 1.
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.
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.
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)].
Our pilot study suggests that the 2G (-1607)MMP-1 genotype may be a potential risk marker of myo- and endometrial hyperplasia.
肌层和子宫内膜的雌激素依赖性增生表现为子宫平滑肌瘤或子宫腺肌病。我们研究了基质金属蛋白酶（MMP）基因常见多态性与子宫增生临床特征之间的可能关联。
观察了170例子宫平滑肌瘤女性患者（46.6±0.5岁）。临床诊断基于体格检查、超声检查和组织学数据。采用白细胞DNA的等位基因特异性聚合酶链反应（PCR）对MMP-1（-1607 1G/2G，rs1799750）和MMP-3（-1171 5A/6A，rs3025058）进行基因分型。使用非参数统计评估临床和遗传数据。
患者和人群对照中MMP-1和MMP-3启动子等位基因的分布相似，符合哈迪-温伯格平衡（HWE）。分别在71%和55%的病例中观察到可检测到的肿瘤生长和子宫腺肌病。稳定状态的平滑肌瘤与MMP-1 1G/1G基因型的较高患病率相关（χ²检验，p = 0.02）。肿瘤生长加速与MMP-1 2G等位基因的较高频率相关[比值比（OR）= 2.048，p = 0.039，χ² = 4.2611，置信区间（CI）=（1.032 - 4.062）]。MMP-1 2G也与多结节生长相关[OR = 3.561，p = 0.01249，χ² = 6.24，CI =（1.261 - 10.058）]。子宫腺肌病患者中MMP-1 2G等位基因有增加趋势[OR = 1.525，p = 0.054，χ² = 3.71，CI =（0.992 - 2.345）]。
我们的初步研究表明，2G（-1607）MMP-1基因型可能是肌层和子宫内膜增生的潜在风险标志物。
