Faculty of Health Sciences, Health Sciences University, Kutahya, Turkey.
Department of Endocrinologyrec, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey.
Prostaglandins Leukot Essent Fatty Acids. 2018 Oct;137:39-42. doi: 10.1016/j.plefa.2018.07.012. Epub 2018 Jul 26.
Type 2 diabetes (T2DM) is caused by the decreased β-cell mass and insulin deficiency, and disease is characterized by hypoglycemia. The insulin resistance also plays an important role in T2DM pathogenesis. Insulin resistance is the reduced biological response to insulin at the normal concentration in the circulation and develops with the influence of environmental factors with genetic abnormalities. In recent years, it has been reported that inflammatory pathway causes activation of the insulin resistance. Chronic inflammation inhibits the insulin sensitivity through activation of signaling pathways which are directly associated with the key components of insulin signaling pathway. Cyclooxygenase (COX) enzymes are key enzymes that catalysis prostaglandin synthesis from arachidonic acid. COX2 is an inducible COX isoform and that plays an important role in inflammatory process by leading the synthesis of pro- and anti- inflammatory prostaglandins. In our study, we aimed to investigate the relationship between variants of COX-2 gene which is one of the key components of the inflammatory pathway, and T2DM risks. In this study, we evaluated rs5275 and rs689466 variants located on the COX-2 gene by PCR-RFLP in 100 T2DM patients and 100 control subjects. The interaction among COX2 variants and T2DM was analyzed using appropriate methods. The both variants were in Hardy-Weinberg equilibrium in patients and controls (p > 0.05). A significant association was observed for genotype distribution of COX2 rs5275 site between control and T2DM cases (p = 0.042). In a dominant model, the cases who had at least one copy of allele C, were at increased risk of T2DM (p = 0.016). We found no significant association for the COX2 rs689466 domain by evaluating homozygous, heterozygous, dominant, and recessive models (p > 0.05). According to our data, the rs5275 variant of the COX2 in the 3'-UTR may contribute to the etiology or modulate the risk of T2DM, whereas the rs689466 variant of the COX2 gene is not associated with T2DM risk.
2 型糖尿病（T2DM）是由β细胞数量减少和胰岛素缺乏引起的，其特征是低血糖。胰岛素抵抗在 T2DM 的发病机制中也起着重要作用。胰岛素抵抗是指在循环中正常浓度的胰岛素下，生物反应降低，并受遗传异常和环境因素的影响而发展。近年来，有报道称炎症途径导致胰岛素抵抗的激活。慢性炎症通过直接与胰岛素信号通路的关键组成部分相关的信号通路的激活来抑制胰岛素敏感性。环氧化酶（COX）酶是催化花生四烯酸合成前列腺素的关键酶。COX2 是一种诱导型 COX 同工酶，通过导致促炎和抗炎前列腺素的合成，在炎症过程中发挥重要作用。在我们的研究中，我们旨在研究炎症途径的关键组成部分之一 COX-2 基因的变体与 T2DM 风险之间的关系。在这项研究中，我们通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）评估了 COX-2 基因上的 rs5275 和 rs689466 变体，在 100 例 T2DM 患者和 100 例对照中进行了评估。通过适当的方法分析了 COX2 变体与 T2DM 之间的相互作用。在患者和对照组中，COX2 变体均处于哈迪-温伯格平衡（p>0.05）。COX2 rs5275 位点的基因型分布在对照组和 T2DM 病例之间存在显著差异（p=0.042）。在显性模型中，至少有一个等位基因 C 的个体患 T2DM 的风险增加（p=0.016）。我们通过评估纯合子、杂合子、显性和隐性模型，发现 COX2 rs689466 区域没有显著相关性（p>0.05）。根据我们的数据，COX2 的 3'-UTR 中的 rs5275 变体可能有助于 T2DM 的病因或调节 T2DM 的风险，而 COX2 基因的 rs689466 变体与 T2DM 风险无关。
