Pituitary Adenylate Cyclase-Activating Peptide-38 in migraine: A systematic review and meta-analysis

Migraine is a complex neurological disorder characterized by recurrent headaches accompanied by sensory disturbances. It involves a combination of genetic, environmental, and neurovascular factors. The objective of this systematic review and meta-analysis was to investigate the correlation between migraine and specific mutant genes by examining the association of Pituitary Adenylate Cyclase-Activating Peptide-38 genes with migraine. A comprehensive search was conducted in major scientific databases, such as PubMed, Scopus, and Embase, to identify relevant studies published up until September 2023. The inclusion criteria encompassed studies that examined the genes (PACAP-38) and various aspects of migraine. Two independent reviewers performed data extraction and quality assessment to ensure the accuracy and reliability of the collected information. Seven studies, comprising 737 patients, were included in the final analysis. The random effects model yielded a standardized mean difference (SMD) of 0.55 (95% CI: -0.15 to 1.25, t=1.45, p=0.19). Heterogeneity among the studies was substantial, with I² indicating 93% variability (95% CI: 84.6% to 96.5%). The heterogeneity was statistically significant (Q= 87.2, df=6, p<0.001). The prediction interval ranged from -1.40 to 2.51. This systematic review and meta-analysis establish a strong link between PACAP-38 and susceptibility to migraine. These findings highlight the significance of genetic factors in migraine development, emphasizing the need for further investigation to elucidate underlying mechanisms and explore the clinical implications of these genetic associations.