Center for Medical Genetics, University of Antwerp.
StatUa Center for Statistics, University of Antwerp, Antwerp.
Psychiatr Genet. 2023 Aug 1;33(4):134-144. doi: 10.1097/YPG.0000000000000339. Epub 2023 May 4.
Tinnitus can be regarded as a chronic stressor, leading to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. There is important comorbidity with anxiety, particularly panic, potentially associated with differences in HPA axis functioning and methylation patterns of HPA axis-related genes. This study examines DNA methylation of the glucocorticoid receptor gene ( NR3C1 ) exon 1F in adults with chronic subjective tinnitus and the possible differential effect of panic.
In a well characterized tinnitus sample ( n = 22, half of which had co-occurring panic attacks), and unaffected controls ( n = 31) methylation patterns of the CpG sites were determined using pyrosequencing and compared between groups through linear mixed models. Gene expression was determined using quantitative PCR on mRNA.
Comparing the combined tinnitus groups to the control group, no DNA methylation differences were observed; however, the tinnitus group with panic attacks showed consistently higher mean methylation values across all CpGs compared to the tinnitus-only and the control group ( P = 0.03 following Tukey correction), which became even more pronounced when accounting for childhood trauma ( P = 0.012). Moreover, a significant positive correlation was found between methylation of the CpG7 site and the Beck Anxiety Inventory total score ( P = 0.001) in the total population. NR3C1 -1F expression was not significantly different between the three groups.
Panic is associated with higher DNA methylation of the NR3C1 exon 1F in adults with chronic subjective tinnitus, consistent with the reduced negative glucocorticoid feedback and HPA axis hyperfunction observed in individuals with panic disorder.
耳鸣可被视为一种慢性应激源，导致下丘脑-垂体-肾上腺（HPA）轴失调。耳鸣与焦虑症，尤其是恐慌症有重要的共病性，可能与 HPA 轴功能和 HPA 轴相关基因的甲基化模式的差异有关。本研究检测了慢性主观性耳鸣成年人的糖皮质激素受体基因（NR3C1）外显子 1F 的 DNA 甲基化情况，以及恐慌症的可能差异影响。
在一个特征明确的耳鸣样本（n ＝ 22，其中一半伴有同时发生的恐慌发作）和未受影响的对照组（n ＝ 31）中，使用焦磷酸测序法确定了 CpG 位点的甲基化模式，并通过线性混合模型比较了组间差异。使用定量 PCR 检测基因表达。
将合并的耳鸣组与对照组进行比较，未观察到 DNA 甲基化差异；然而，伴有恐慌发作的耳鸣组与仅耳鸣组和对照组相比，所有 CpG 位点的平均甲基化值均持续升高（Tukey 校正后 P ＝ 0.03），当考虑到儿童期创伤时，这种差异更为明显（P ＝ 0.012）。此外，在总人群中，还发现 CpG7 位点的甲基化与贝克焦虑量表总分呈显著正相关（P ＝ 0.001）。NR3C1-1F 的表达在三组之间无显著差异。
在患有慢性主观性耳鸣的成年人中，恐慌症与 NR3C1 外显子 1F 的 DNA 高甲基化有关，这与恐慌障碍个体中观察到的负性糖皮质激素反馈减少和 HPA 轴功能亢进一致。
