Expression of NF-κB-associated lncRNAs in different types of migraine.

Abstract

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.