Original Article

A pilot study of FOXP3 Gene (rs2232365, rs3761547, and rs3761548) Mutations in Migraine Patients

Abstract

 

Background: The role of immune dysfunction in migraine pathogenesis is currently debated. Migraines are common among family members, yet no significant gene polymorphisms have been identified to date. However, our earlier clinical study findings led us to hypothesize that migraine initiation could be influenced by genes that regulate immune function, specifically Forkhead box P3 (FOXP3). To test this hypothesis, we conducted a pilot study targeting FOXP3 Single Nucleotide Polymorphisms (SNPs), commonly associated with other autoimmune conditions in patients with migraine. Materials and Methods: The minimum sample size required for this study was determined by considering the mean difference in Regulatory T cells (Tregs) reduction reported in previous studies. Twenty participants (10 patients and 10 controls) were recruited for this study. Familial clinical history was collected for pedigree analysis and the samples were tested for the targeted SNPs. Results: The prevalence of the AG genotype for rs2232365 was 50% among patients and 20% among controls (OR: 4.0, CI: 0.54-29.09, p=0.17). Regarding rs3761547, the AG genotype was observed in 60% of patients and 10% of controls (OR: 13.5, CI: 1.19-152.2, p=0.03), whereas the AC genotype was found in 70% of patients and only 10% of controls (OR: 21.0, CI: 1.77-248.1, p=0.01). Conclusion: Our preliminary analysis suggested a possible association between FOXP3 variance and migraine predisposition, particularly with the AG and AC genotypes at the rs3761547 and rs3761548 SNPs, respectively. These findings highlight the importance of conducting a more extensive FOXP3 mutation study in a larger cohort of migraine patients.

1. Steiner TJ, Stovner LJ, Vos T. GBD 2015: migraine is the third cause of disability in under 50s. J Headache Pain. 2016;17(1):104.
2. Lateef TM, Cui L, Nakamura E, Dozier J, Merikangas K. Accuracy of family history reports of migraine in a community-based family study of migraine. Headache. 2015;55(5):597-603.
3. Kulkarni GB, Rao GN, Gururaj G, Stovner LJ, Steiner TJ. Headache disorders and public ill-health in India: prevalence estimates in Karnataka State. J Headache Pain. 2015;16(1):71.
4. Joshi SS, Apoorva RP, Vijayalaxmi. Clinical profile of migraine in a rural population presenting to a tertiary care hospital in South India. Int J Acad Med Pharm. 2023;5(1):111-115..
5. Grangeon L, Lange KS, Waliszewska-Prosó? M, et al. Genetics of migraine: where are we now? J Headache Pain. 2023;24(1):23.
6. Stuart S, Cox HC, Lea RA, Griffiths LR. The role of the MTHFR gene in migraine. Headache. 2012;52(10):1644-1651.
7. Grieco GS, Gagliardi S, Ricca I, et al. New CACNA1A deletions are associated to migraine phenotypes. J Headache Pain. 2018;19(1):75.
8. Gormley P, Kurki MI, Hiekkala ME, et al. Common variant burden contributes to the familial aggregation of migraine in 1,589 families. Neuron. 2018;99(4):711-722.e6.
9. Arumugam M, Narayan S. Rethinking of the concepts: Migraine is an autoimmune disease? Neurol Psychiatry Brain Res. 2019;34:26-31.
10. Sutherland HG, Albury CL, Griffiths LR. Advances in genetics of migraine. J Headache Pain. 2019;20(1):94.
11. Faraji F, Mosayebi G, Bahrami M, et al. rs3761548 (C/A) and rs5902434 (del/ATT) polymorphisms of Foxp3 gene in Iranian patients with migraine. Egypt J Med Hum Genet. 2023;44(1):3.
12. Arumugam M, Sugumar S, Ganesan P. The initiation of a migraine associated with a specific gene responsible for regulating immune function: Hypothesis. Med Hypotheses. 2024;174:111382.
13. Arumugam M, Parthasarathy V. Reduction of CD4(+)CD25(+) regulatory T-cells in migraine: Is migraine an autoimmune disorder? J Neuroimmunol. 2016;295:1-6.
14. Lee EC, Whitehead AL, Jacques RM, Julious SA. The statistical interpretation of pilot trials: should significance thresholds be reconsidered? BMC Med Res Methodol. 2014;14:41.
15. Sullivan L. Power and Sample Size Determination. Boston University School of Public Health. Power and Sample Size Determination. Available from: https://www.bu.edu/sph.
16. Faraji F, Shojapour M, Farahani I, Ganji A, Mosayebi G. Reduced regulatory T lymphocytes in migraine patients. Neurol Res. 2021;43(3):187-193.
17. Li H, Fu Q, Philips K, et al. Leukocyte inflammatory phenotype and function in migraine patients compared with matched non-migraine volunteers: a pilot study. BMC Neurol. 2022;22(1):282.
18. Diener HC, Tassorelli C, Dodick DW, et al. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019;39(7):694-703.
19. Mohr A, Malhotra R, Mayer G, Gorochov G, Miyara M. Human FOXP3+ T regulatory cell heterogeneity. Clin Transl Immunol. 2018;7(4):e1005.
20. Phillips R. FOXP3 splice variant is associated with autoimmune disease. Nat Rev Rheumatol. 2022;18(11):713-714.
Files
IssueVol 7, No 4 (2024) QRcode
SectionOriginal Article
DOI https://doi.org/10.18502/igj.v7i4.17892
Keywords
Migraine FOXP3 Gene Immune Dysregulation Regulatory T Cells utoimmune Disorders Genetic Mutation
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Sugumar S, A Suresh J, Avadhani D, Hazeena P, Arumugam M. A pilot study of FOXP3 Gene (rs2232365, rs3761547, and rs3761548) Mutations in Migraine Patients. Immunol Genet J. 2024;7(4):274-280.