Department of Immunology, Medical University of Gdańsk, ul. Dębinki 1, 80-211, Gdańsk, Poland.
Chair & Clinics of Paediatrics, Diabetology and Endocrinology, Medical University of Gdańsk, Dębinki 7, 80-211, Gdańsk, Poland.
Mol Cell Biochem. 2018 Jan;437(1-2):153-161. doi: 10.1007/s11010-017-3103-0. Epub 2017 Jun 20.
The effect of estrogens is mediated by activation of estrogen receptors (ERs). Because ER-α gene polymorphisms may exert different effects in childhood, we analyzed the associations between the IVS1 -397T>C (PvuII) polymorphism and systemic inflammatory state, proangiogenic factors, frequency of monocyte subsets, lipid profile, blood pressure, and vascular complications in girls with type 1 diabetes mellitus (DM1). We examined 180 young girls with DM1 and 120 healthy age-matched controls. The analysis concerned PvuII polymorphism of the ER-α gene as well as the levels of serum inflammatory markers (CRP, IL-6, TNF-α), proangiogenic factors (VEGF, angiogenin), 17β-estradiol, values of monocyte subsets (CD14CD16 and CD14CD16), lipid profile, and blood pressure. In our study, girls with CC genotype had lower level of inflammatory and angiogenic factors and lower frequencies of CD14CD16 monocytes in comparison to CT or TT carriers. Simultaneously, the CC carriers had a greater population of CD14CD16 monocytes, increased blood pressure, and serum levels of: estrogen, total cholesterol, triglycerides, and low-density lipoprotein cholesterol than girls bearing CT or TT genotype. Our study suggests a pleiotropic effect of PvuII polymorphic CC variant on diabetic vasculopathies. Although the CC genotype carriers demonstrate less inflammatory and angiogenic activity, they seem to display less favorable cardiometabolic features. Based on our study, we cannot distinguish PvuII ER-α genotype that could be useful in identification of DM1 girls that are more prone to develop of late vascular complications, before the occurrence of first clinical symptoms.
雌激素的作用是通过激活雌激素受体 (ER) 来介导的。由于 ER-α 基因多态性可能在儿童期产生不同的影响,我们分析了 IVS1-397T>C(PvuII)多态性与系统性炎症状态、促血管生成因子、单核细胞亚群频率、血脂谱、血压和 1 型糖尿病 (DM1) 女孩的血管并发症之间的关系。我们检查了 180 名患有 DM1 的年轻女孩和 120 名年龄匹配的健康对照者。该分析涉及 ER-α 基因的 PvuII 多态性以及血清炎症标志物 (CRP、IL-6、TNF-α)、促血管生成因子 (VEGF、血管生成素)、17β-雌二醇、单核细胞亚群 (CD14CD16 和 CD14CD16) 的水平、血脂谱和血压。在我们的研究中,与 CT 或 TT 携带者相比,CC 基因型的女孩具有较低水平的炎症和血管生成因子以及较低频率的 CD14CD16 单核细胞。同时,CC 携带者的 CD14CD16 单核细胞数量更多,血压升高,血清雌激素、总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平也高于携带 CT 或 TT 基因型的女孩。我们的研究表明 PvuII 多态性 CC 变体对糖尿病血管病变具有多效性影响。尽管 CC 基因型携带者表现出较少的炎症和血管生成活性,但它们似乎表现出不太有利的心脏代谢特征。基于我们的研究,我们无法区分 PvuII ER-α 基因型,该基因型可能有助于识别更容易发生晚期血管并发症的 DM1 女孩,而无需出现首发临床症状。