Association between TNFa rs1800629 and migraine: Case-control study and updated meta-analysis

Migraine is a multifactorial disorder influenced by both genetic and environmental factors. In this study, we aimed to explore the association of tumor necrosis factor alpha (TNFa) rs1800629 with migraine susceptibility. A case-control study design was employed to assess this association in individuals of Greek ancestry. Subsequently, a meta-analysis of published studies was conducted, thereby incorporating the findings of the present study to further evaluate the relationship between rs1800629 and a migraine. A total of 123 patients with migraines (44.4 ± 10.3 years, 105 women) and an even number of healthy controls (HC) (58.7 ± 12.0 years, 76 women) were recruited. TNFa rs1800629 was in Hardy-Weinberg equilibrium among the HC (P = 1.00). No association was observed between TNFa rs1800629 and migraines under any genetic model. Additional, subgroup analyses stratified by sex and migraine subtype showed no associations. The meta-analysis, comprised of 14,742 participants with migraines and 46,384 HC, indicated a trend towards a risk-conferring effect of rs1800629 [Odds ratio (OR) = 1.26, 95% confidence interval (95% CI) = (0.97-1.64), P = 0.09]. Subgroup analyses revealed a significant association in individuals of Asian ancestry [OR = 1.64, 95% CI = (1.08-2.48), P = 0.02]. Additionally, the over-dominant model was related to migraines with aura [OR = 1.21, 95% CI = (1.08-1.35), P = 0.001]. Subgroup analyses for men and women, as well as for migraines without aura, were insignificant. This case-control study provides evidence that the TNFa rs1800629 polymorphism is not associated with migraine susceptibility in the Greek population. The updated meta-analysis showed that rs1800629 increases migraine risk in individuals of Asian ancestry. These findings support a population-specific genetic effect. Finally, the observed association with migraine with aura under the over-dominant model may indicate a heterozygote-driven effect. Given the extremely low frequency of homozygosity for the minor allele, this result should be interpreted with caution.