Enlightening the association between TNF-α -308 G > A and migraine: a meta-analysis with meta-regression and trial sequential analysis

BACKGROUND: Migraine is a complex neurological disorder that is characterized by a "lower threshold of neuronal hyperexcitability" with distinctive periodicity and complex vascular dysfunction. Genetic factors have impacted incredibly on the susceptibility of migraine and one such example is the TNF-α 308G > A. AIM: Therefore, we aim to provide a glimpse of the association of the TNF-α 308G > A risk on the susceptibility of migraine. METHOD: The pooled odds ratio with the associated 95% of confidence interval were calculated using different genetic models. Heterogeneity was accessed by using Cochran's Q Test and I(2) statistics and Begg's and Egger's tests were used for finding the publication bias, tests were two-sided, and a p-value of < 0.05 was considered statistically significant. The Trial Sequential Analysis with Meta-regression Analysis were also utilized to find out the sample size requirement for meta-analysis to avoid type I error and source of heterogeneity respectively. RESULT: A total of 13 studies with cases: 7193 and controls: 23,091 were included and after using different genetic models, no overall association with migraine and its clinical subtype migraine with aura was observed (Allele model “OR: 1.28, 95% C.I. [0.96–1.69] and OR: 0.99,95% C.I. [0.69–1.42]) respectively. Interestingly, after sub-grouping using the “ethnicity criteria” in the migraine group, it was observed that the allelic genetic model and the dominant model were found to be significantly associated with the Asian ethnic group (OR: 1.79, 95% C.I. [1.13–2.84], and OR: 1.85, 95% C.I. [1.0927; 3.1580]. CONCLUSION: In conclusion, the present meta-analysis has provided evidence that 308G > A increases the risk of migraine only in the Asian population.