The Power of WNT5A and FZD3 Gene Expression and Methylation Status in the Diagnosis-Treatment-Cause Triangle in Tension-Type Headache.

DNA methylation is the epigenetic pathway controlling cellular gene expression. Methylation is a natural and cellular epigenetic mechanism for gene silencing. The fact that the genes that the cell decides to be silent do not speak or begin to speak may coincide with diseases. For explanatory evidence, changes at the DNA level can provide realistic information. Wnt/β-catenin signaling has an important role in the pain process. For this purpose, we investigated the relationship between clinical data, wingless-type MMTV integration site family, member 5A (WNT5A), and Frizzled Class Receptor 3 (FZD3) gene methylation and expression in a cohort of tension-type headache (TTH) patients (N = 130) and healthy control (N = 117) individuals. Comorbidities were evaluated. Methylation profiling was performed using Real-Time PCR with a TaqMan primer-probe. The diagnostic power (receiver operating characteristic-ROC) was determined according to the expression and methylation status. Ultimately, WNT5A was found to be upregulated and hypermethylated, and FZD3 was found to be upregulated and hypomethylated. Finally, the area under the curve (AUC) data for FZD3 upregulation (0.983) and hypomethylation (0.866) showed diagnostic values. WNT5A and FZD3 may contribute to the pathogenesis of the disease depending on their expression and methylation profile during the TTH process. At the same time, diagnostic powers have the potential to be a resource for early treatment and new therapeutic approaches.