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

Ioannis Liampas; Maria Papasavva; Silvia Demiri; Michail Vikelis; Chrysoula Marogianni; Evripidis Vlachakis; Emmanouil V Dermitzakis; Aristidis Tsatsakis; Nikolaos Drakoulis; Efthimios Dardiotis; Vasileios Siokas; Ioannis Liampas; Maria Papasavva; Silvia Demiri; Michail Vikelis; Chrysoula Marogianni; Evripidis Vlachakis; Emmanouil V Dermitzakis; Aristidis Tsatsakis; Nikolaos Drakoulis; Efthimios Dardiotis; Vasileios Siokas

doi:10.3934/Neuroscience.2026013

AIMS Neuroscience

2026, Volume 13, Issue 2: 295-315. doi: 10.3934/Neuroscience.2026013

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Research article

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

1.
Department of Neurology, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Mezourlo Hill, 41110 Larissa, Greece
2.
Laboratory of Neurogenetics, University of Thessaly, Mezourlo Hill, 41110 Larissa, Greece
3.
Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia, Cyprus
4.
Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece
5.
School of Medicine, University of Patras, Rio Patras 26504, Greece
6.
Headache Clinic, Mediterraneo Hospital, 166 75 Glifada, Greece
7.
Euromedica General Clinic, 546 45 Thessaloniki, Greece
8.
Center of Toxicology & Science Applications, Medical School, University of Crete, 71003 Heraklion, Greece
9.
Universidad Ecotec, Km. 13.5 Samborondon, EC 092302 Samborondon, Ecuador
10.
Sechenov IM, First State Medical University, 119991 Moscow, Russia
Shared senior authorship.

Received: 12 December 2025 Revised: 11 April 2026 Accepted: 22 April 2026 Published: 29 May 2026

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.
- migraine,
- rs1800629,
- TNFa,
- SNP,
- polymorphism
Citation: Ioannis Liampas, Maria Papasavva, Silvia Demiri, Michail Vikelis, Chrysoula Marogianni, Evripidis Vlachakis, Emmanouil V Dermitzakis, Aristidis Tsatsakis, Nikolaos Drakoulis, Efthimios Dardiotis, Vasileios Siokas. Association between TNFa rs1800629 and migraine: Case-control study and updated meta-analysis[J]. AIMS Neuroscience, 2026, 13(2): 295-315. doi: 10.3934/Neuroscience.2026013

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Abstract

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.

Acknowledgments

Funding: This research received no external funding. Institutional Review Board Statement: The studies involving human participants were reviewed and approved by Ethics Committee of Mediterraneo Hospital, Glyfada, Greece and University Hospital of Larissa Ethics Committee.
Informed Consent Statement: The patients/participants provided their written informed consent to participate in this study.

Conflict of interest

The authors declare no conflict of interest.

Authors' contributions

Ioannis Liampas, methodology, investigation, formal analysis, writing—original draft preparation; Maria Papasavva, conceptualization, methodology, validation, investigation, formal analysis, writing—review and editing; Silvia Demiri, methodology, investigation, data curation, writing—original draft preparation; Michail Vikelis, validation, writing—review and editing; Chrysoula Marogianni, investigation, writing—review and editing; Evripidis Vlachakis, investigation, writing—review and editing; Emmanouil V Dermitzakis, validation, writing—review and editing; Aristidis Tsatsakis, validation, writing—review and editing; Nikolaos Drakoulis, validation, writing—review and editing, supervision; Efthimios Dardiotis, conceptualization, writing—review and editing, supervision; Vasileios Siokas, conceptualization, writing—review and editing, supervision. All authors have read and agreed to the published version of the manuscript.

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