The holistic approach to theCHRNA7gene,hsa-miR-3158-5p, and 15q13.3 hotspot CNVs in migraineurs

Abstract

Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit ( CHRNA7) gene, and expression of gene-targeting miRNAs ( hsa-miR-548e-5p and hsa-miR-3158-5p) in migraineurs ( n = 102; with aura, n = 43; without aura, n = 59) and non-migraines ( n = 120) aged 15–60 years, comparative, case–control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2−ΔΔCTmethod. The diagnostic power of the CHRNA7 gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). CHRNA7 gene and hsa-miR-3158-5p are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs ( p < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers ( p = .05). The number of CNV deletions was higher than duplications. When CHRNA7-CNV- hsa-miR-3158-5p was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was “good”. In migraineurs, the CHRNA7 gene can be controlled by hsa-miR-3158-5p via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.