Eyileten Ceren, Zaremba Małgorzata, Janicki Piotr K, Rosiak Marek, Cudna Agnieszka, Kapłon-Cieślicka Agnieszka, Opolski Grzegorz, Filipiak Krzysztof J, Kosior Dariusz A, Mirowska-Guzel Dagmara, Postula Marek
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, Warsaw, Poland.
Perioperative Genomics Laboratory, Penn State University, College of Medicine, Hershey, PA, USA.
Med Sci Monit. 2016 Jan 7;22:69-76. doi: 10.12659/msm.895607.
The aim of this study was to investigate the association between serum concentrations of the brain-derived neurotrophic factor (BDNF), platelet reactivity and inflammatory markers, as well as its association with BDNF encoding gene variants in type 2 diabetic patients (T2DM) during acetylsalicylic acid (ASA) therapy.
MATERIAL/METHODS: This retrospective, open-label study enrolled 91 patients. Serum BDNF, genotype variants, hematological, biochemical, and inflammatory markers were measured. Blood samples were taken in the morning 2-3 h after the last ASA dose. The BDNF genotypes for selected variants were analyzed by use of the iPLEX Sequenom assay.
In multivariate linear regression analysis, CADP-CT >74 sec (p<0.001) and sP-selectin concentration (p=0.03) were predictive of high serum BDNF. In multivariate logistic regression analysis, CADP-CT >74 sec (p=0.02) and IL-6 concentration (p=0.03) were risk factors for serum BDNF above the median. Non-significant differences were observed between intronic SNP rs925946, missense SNP rs6265, and intronic SNP rs4923463 allelic groups and BDNF concentrations in the investigated cohort.
Chronic inflammatory condition and enhanced immune system are associated with the production of BDNF, which may be why the serum BDNF level in T2DM patients with high platelet reactivity was higher compared to subjects with normal platelet reactivity in this study.
本研究旨在探讨2型糖尿病患者（T2DM）在乙酰水杨酸（ASA）治疗期间血清脑源性神经营养因子（BDNF）浓度、血小板反应性与炎症标志物之间的关联，以及其与BDNF编码基因变异的关系。
材料/方法：这项回顾性、开放标签研究纳入了91例患者。检测血清BDNF、基因变异、血液学、生化和炎症标志物。在最后一剂ASA后2 - 3小时的早晨采集血样。使用iPLEX Sequenom分析方法分析所选变异的BDNF基因型。
在多变量线性回归分析中，CADP - CT>74秒（p<0.001）和可溶性P选择素浓度（p = 0.03）可预测高血清BDNF。在多变量逻辑回归分析中，CADP - CT>74秒（p = 0.02）和白细胞介素-6浓度（p = 0.03）是血清BDNF高于中位数的危险因素。在所研究队列中，内含子SNP rs925946、错义SNP rs6265和内含子SNP rs4923463等位基因组与BDNF浓度之间未观察到显著差异。
慢性炎症状态和增强的免疫系统与BDNF的产生有关，这可能就是本研究中血小板反应性高的T2DM患者血清BDNF水平高于血小板反应性正常患者的原因。
