Ebrahimi Arezou, Hosseinzadeh Colagar Abasalt, Karimian Mohammad
Department of Biology, Faculty of Sciences, Islamic Azad University, Damghan Branch, Damghan, Iran. AND Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
Acta Med Iran. 2017 May;55(5):297-303.
Methionine synthase (MTR) is one of the key enzymes of folate pathway, which play a key role in the construction, repair, and methylation of DNA. In this study, an association of MTR A2756G gene transition with prostate cancer in men populations of Kashan-Iran was investigated by a case-control study and an in silico analysis. The 200 samples including 100 patients with prostate cancer, as case group and 100 healthy men, as control group included in this study. MTR-A2756G genotyping was performed by PCR-RFLP technique. Some in silico tools used to evaluate the effects of A2756G transition on the structure and function of MTR. Results showed that the AG genotype (OR: 2.4014, 95% CI: 1.3216-4.3636, P=0.0040), and GG genotype (OR: 3.6324, 95% CI: 1.2629-10.4475, P=0.0167) and G allele (OR: 2.0120, 95% CI: 1.3098-3.0905, P=0.0014) were associated with prostate cancer. In silico analysis showed that polymorphisms of the enzyme protein might change properties of MTR such as relative mutability and flexibility, which leads to alteration of stability and function of the enzyme. Based on the results, an MTR-A2756G polymorphism which changes activity and stability of the methionine synthase associated with prostate cancer in men. It is a preliminary study and is presenting data for future comprehensive study for making a clinical conclusion that this gene transition is a biomarker for susceptibility to prostate cancer.
甲硫氨酸合成酶(MTR)是叶酸代谢途径的关键酶之一,在DNA的构建、修复和甲基化过程中发挥关键作用。在本研究中,通过病例对照研究和计算机模拟分析,对伊朗卡尚男性人群中MTR A2756G基因转换与前列腺癌的相关性进行了调查。本研究纳入了200个样本,其中100例前列腺癌患者作为病例组,100名健康男性作为对照组。采用PCR-RFLP技术进行MTR-A2756G基因分型。使用一些计算机模拟工具来评估A2756G转换对MTR结构和功能的影响。结果显示,AG基因型(比值比:2.4014,95%置信区间:1.3216 - 4.3636,P = 0.0040)、GG基因型(比值比:3.6324,95%置信区间:1.2629 - 10.4475,P = 0.0167)和G等位基因(比值比:2.0120,95%置信区间:1.3098 - 3.0905,P = 0.0014)与前列腺癌相关。计算机模拟分析表明,该酶蛋白的多态性可能会改变MTR的特性,如相对突变性和灵活性,从而导致酶的稳定性和功能发生改变。基于这些结果,MTR-A2756G多态性改变了甲硫氨酸合成酶的活性和稳定性,与男性前列腺癌相关。这是一项初步研究,为未来全面研究提供数据,以得出该基因转换是前列腺癌易感性生物标志物的临床结论。