Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Acta Neurol Belg. 2023 Oct;123(5):1823-1831. doi: 10.1007/s13760-022-02071-3. Epub 2022 Sep 6.
NF-κB partakes in the pathophysiology of neurologic conditions. We quantified levels of NF-κB-associated genes in 119 patients with migraine versus healthy controls.
We measured levels of NF-κB-associated genes in 42 patients with migraine compared with age- and sex-matched controls.
Comparison between patients without aura and controls revealed down-regulation of PACER [expression ratio (95% CI) 0.15 (0.06-0.36), P value < 0.0001]. Similar results were detected when comparing expression of PACER in patients with aura and controls [expression ratio (95% CI) 0.05 (0.02-0.12), P value < 0.0001]. Both DILC and CEBPA were over-expressed in patients with aura [expression ratio (95% CI) 4.9 (2.96-7.83), P value < 0.0001 and expression ratio (95% CI) 3.65 (2.39-5.24), P value < 0.0001, respectively] and in patients without aura compared with controls [expression ratio (95% CI) 3.6 (2.21-5.69), P value < 0.0001 and expression ratio (95% CI) 4.5 (2.53-7.11), P value < 0.0001, respectively]. ADINR was over-expressed in patients with aura [expression ratio (95% CI) 4.98 (3.09-8.33), P value < 0.0001] as well as patients without aura compared with controls [expression ratio (95% CI) 13.15 (7.41-23.58), P value < 0.0001]. Notably, ADINR levels were lower in patients with aura compared with patients without aura. When comparing ATG5 levels in patients with aura and controls, significant up-regulation was detected [expression ratio (95% CI) 4.4 (3.01-6.32), P value < 0.0001]. This pattern was also detected in patients without aura compared with controls [expression ratio (95% CI) 3.5 (2.28-5.35), P < 0.0001]. Finally, expression of DICER1-AS1 was elevated in patients with aura compared with patients without aura [expression ratio (95% CI) 2.47 (1.14-5.85), P = 0.03]. This lncRNA was under-expressed in patients without aura compared with controls [expression ratio (95% CI) 0.4 (0.21-1.31), P = 0.03]. CEBPA, ATG5 and ADINR had the best AUC values for distinguishing patients with aura from controls (AUC values = 0.91, 0.85 and 0.83, respectively). The AUC values for separation between patients without aura and controls were 0.90, 0.86 and 0.75 for CEBPA, ATG5 and ADINR, respectively.
Taken together, several genes in the NF-κB pathway has been revealed to be dysregulated in migraineurs and expression of these genes can be used as markers for this neurological condition.
NF-κB 参与神经疾病的病理生理学。我们定量测定了 119 例偏头痛患者和健康对照者的 NF-κB 相关基因水平。
我们比较了 42 例偏头痛患者和年龄、性别匹配的对照组患者 NF-κB 相关基因的水平。
与对照组相比，无先兆偏头痛患者 PACER 的表达下调[表达比（95%可信区间）0.15（0.06-0.36），P 值<0.0001]。与对照组相比，有先兆偏头痛患者 PACER 的表达也存在类似的下调[表达比（95%可信区间）0.05（0.02-0.12），P 值<0.0001]。DILC 和 CEBPA 在有先兆偏头痛患者[表达比（95%可信区间）4.9（2.96-7.83），P 值<0.0001和表达比（95%可信区间）3.65（2.39-5.24），P 值<0.0001]和无先兆偏头痛患者[表达比（95%可信区间）3.6（2.21-5.69），P 值<0.0001和表达比（95%可信区间）4.5（2.53-7.11），P 值<0.0001]中均过表达。ADINR 在有先兆偏头痛患者[表达比（95%可信区间）4.98（3.09-8.33），P 值<0.0001]和无先兆偏头痛患者[表达比（95%可信区间）13.15（7.41-23.58），P 值<0.0001]中过表达。值得注意的是，与无先兆偏头痛患者相比，有先兆偏头痛患者的 ADINR 水平较低。与对照组相比，ATG5 在有先兆偏头痛患者中显著上调[表达比（95%可信区间）4.4（3.01-6.32），P 值<0.0001]。在无先兆偏头痛患者中也存在类似的上调[表达比（95%可信区间）3.5（2.28-5.35），P 值<0.0001]。最后，与无先兆偏头痛患者相比，有先兆偏头痛患者 DICER1-AS1 的表达升高[表达比（95%可信区间）2.47（1.14-5.85），P 值=0.03]。与对照组相比，无先兆偏头痛患者 DICER1-AS1 的表达下调[表达比（95%可信区间）0.4（0.21-1.31），P 值=0.03]。CEBPA、ATG5 和 ADINR 对区分有先兆偏头痛患者和对照组具有最佳的 AUC 值（AUC 值分别为 0.91、0.85 和 0.83）。CEBPA、ATG5 和 ADINR 对无先兆偏头痛患者和对照组的 AUC 值分别为 0.90、0.86 和 0.75。
综上所述，NF-κB 通路中的几个基因在偏头痛患者中存在失调，这些基因的表达可以作为该神经疾病的标志物。
