Department of Medical Genetics, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey.
Faculty of Engineering, Aydin Adnan Menderes University, Aydin, Turkey.
Mol Biol Rep. 2019 Aug;46(4):3929-3936. doi: 10.1007/s11033-019-04837-0. Epub 2019 Apr 30.
Brain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) are neurotrophic factors that play key roles in the auditory pathway. While the relationship between serum levels and polymorphisms of BDNF/GDNF and chronic tinnitus is emphasized in the literature, there is no study showing the link between the promoter methylations of these genes and tinnitus. For this purpose, the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations was investigated to identify their role in the pathophysiology of tinnitus. In this case-control study, we examined the possible effects of BDNF/GDNF methylations in the blood samples of patients with tinnitus complaints for more than 3 months. Sixty tinnitus subjects between the ages of 18-55 and 50 healthy control subjects in the same age group who were free of any otorhinolaryngology and systemic disease were selected for examination. Methylation of total 12 CpG sites in BDNF and GDNF promoter regions were determined by the bisulfite-pyrosequencing method. Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5-6 methylation ratios in the comparison of control group and the chronic tinnitus patients (P = 0.002, 0.0005, 0.00003, and 0.0029, respectively). To our knowledge, this is the first study in the literature investigating the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations. It is believed that the current results might be supported by investigating the relationships between BDNF/GDNF methylations and genotypes in future research using higher sample sizes.
脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）是在听觉通路中发挥关键作用的神经营养因子。尽管文献强调了血清水平与 BDNF/GDNF 的多态性之间的关系以及慢性耳鸣，但尚无研究表明这些基因启动子甲基化与耳鸣之间存在联系。为此，研究了慢性耳鸣与外周血衍生的 BDNF/GDNF 启动子甲基化之间的关系，以确定它们在耳鸣病理生理学中的作用。在这项病例对照研究中，我们检查了耳鸣患者超过 3 个月的外周血样本中 BDNF/GDNF 甲基化的可能影响。在年龄为 18-55 岁的耳鸣患者和年龄相匹配的 50 名无耳科和全身疾病的健康对照组中，共检查了 60 名耳鸣患者。通过亚硫酸氢盐-焦磷酸测序法测定 BDNF 和 GDNF 启动子区域的 12 个 CpG 位点的甲基化情况。在对照组和慢性耳鸣患者的比较中，BDNF CpG6 和 GDNF CpG3-5-6 甲基化比率存在统计学显著差异（P=0.002、0.0005、0.00003 和 0.0029）。据我们所知，这是文献中首次研究慢性耳鸣与外周血衍生的 BDNF/GDNF 启动子甲基化之间的关系。相信在未来的研究中，使用更大的样本量，调查 BDNF/GDNF 甲基化与基因型之间的关系，可能会支持当前的结果。
