Tarki Saeedeh Ebrahimi, Far Iman Salahshouri, Aminimoghaddam Soheila, Fooladi Bahareh, Sarhangi Negar, Farahani Maryam Shahrabi, Klashami Zeynab Nickhah, Hamidi Armita Kakavand, Amoli Mahsa Mohammad
Department of Genetics, School of Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biology, School of Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Eur J Obstet Gynecol Reprod Biol. 2021 Mar;258:353-357. doi: 10.1016/j.ejogrb.2020.12.013. Epub 2020 Dec 10.
matrix metalloproteinases including matrix metalloproteinase-2 play a key role in endometrial extra cellular matrix breakdown in endometriosis. Aberrant expression of matrix metalloproteinase-2 has been reported in eutopic and ectopic endometrial tissue of endometriosis patients so altered expression of matrix metalloproteinase-2 due to polymorphisms may lead to establishment and progression of endometriosis. In this study the association between -735 C/T (rs2285053) and -1575 G/A (rs243866) variants of matrix metalloproteinase-2 gene with presence of endometriosis in an Iranian population were investigated for the first time.
A case-control association study was conducted to investigate the role of MMP-2-735 C/T and _1575 G/A variants in development of endometriosis. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine genotype frequencies of these variants in 100 endometriosis patients and 200 normal samples. Total genomic DNA was extracted from blood samples and single-nucleotide polymorphism flanking regions were amplified using designed specific primers. Enzymatic digestion was performed using Pag I and Hinf I restriction enzymes for rs2285053 and rs243866 variants, respectively. Statistical analysis was ascertained using statistical package for social science version 16 and "SHEsis" software.
There were no significant differences in genotype frequencies of rs2285035 (-735C/T) variant between case and control groups (CC + CT vs. TT p = 0.40; OR = 0.50, 95 % CI 0.100-2.551). There were also no significant differences for C allele frequencies in both case and control groups (p = 0.9). For variant rs243866 (-1575 G/A) the differences in genotype frequencies between case and controls group were determined to be significant (GG + GA vs. AA p = 0.041; OR = 6.46, 95 % CI 0.82-50.43). The frequency of G allele was significantly different in case and control groups (p = 0.037).
In conclusion, existence of rs243866 variant in promoter region of matrix metalloproteinase-2 gene can increase the risk of endometriosis in Iranian women.
包括基质金属蛋白酶-2在内的基质金属蛋白酶在子宫内膜异位症的子宫内膜细胞外基质分解中起关键作用。据报道，子宫内膜异位症患者的在位和异位子宫内膜组织中基质金属蛋白酶-2表达异常，因此，由于基因多态性导致的基质金属蛋白酶-2表达改变可能会导致子宫内膜异位症的发生和发展。在本研究中，首次在伊朗人群中研究了基质金属蛋白酶-2基因的-735 C/T（rs2285053）和-1575 G/A（rs243866）变体与子宫内膜异位症的关系。
进行了一项病例对照关联研究，以调查MMP-2 -735 C/T和-1575 G/A变体在子宫内膜异位症发生中的作用。采用聚合酶链反应-限制性片段长度多态性方法测定100例子宫内膜异位症患者和200例正常样本中这些变体的基因型频率。从血样中提取总基因组DNA，并使用设计的特异性引物扩增单核苷酸多态性侧翼区域。分别使用Pag I和Hinf I限制性内切酶对rs2285053和rs243866变体进行酶切消化。使用社会科学统计软件包第16版和“SHEsis”软件进行统计分析。
病例组和对照组之间rs2285035（-735C/T）变体的基因型频率无显著差异（CC + CT与TT相比，p = 0.40；OR = 0.50，95%CI 0.100 - 2.551）。病例组和对照组的C等位基因频率也无显著差异（p = 0.9）。对于rs243866（-1575 G/A）变体，病例组和对照组之间的基因型频率差异具有统计学意义（GG + GA与AA相比），p = 0.041；OR = 6.46，95%CI 0.82 - 50.43）。病例组和对照组的G等位基因频率有显著差异（p = 0.037）。
总之，基质金属蛋白酶-2基因启动子区域存在rs243866变体可增加伊朗女性患子宫内膜异位症的风险。
