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Timasheva Ya.R.

Ufa Federal Research Centre of the Russian Academy of Sciences;
Bashkir State Medical University

Nasibullin T.R.

Ufa Federal Research Centre of the Russian Academy of Sciences

Tuktarova I.A.

Ufa Federal Research Centre of the Russian Academy of Sciences

Erdman V.V.

Ufa Federal Research Centre of the Russian Academy of Sciences

Vashenko V.I.

Ufa Federal Research Centre of the Russian Academy of Sciences

Galiullin T.R.

Bashkir State Medical University

Lyutov O.V.

Bashkir State Medical University

Bakhtiiarova K.Z.

Bashkir State Medical University

Search for informative predictors of the development and progression of multiple sclerosis

Authors:

Timasheva Ya.R., Nasibullin T.R., Tuktarova I.A., Erdman V.V., Vashenko V.I., Galiullin T.R., Lyutov O.V., Bakhtiiarova K.Z.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(9): 124‑130

DOI: 10.17116/jnevro2025125091124

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Table of contents

SEARCH FOR INFORMATIVE PREDICTORS OF THE DEVELOPMENT AND PROGRESSION OF MULTIPLE SCLEROSIS
SEARCH FOR INFORMATIVE PREDICTORS OF THE DEVELOPMENT AND PROGRESSION OF MULTIPLE SCLEROSIS

To cite this article:

Timasheva YaR, Nasibullin TR, Tuktarova IA, et al. . Search for informative predictors of the development and progression of multiple sclerosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(9):124‑130. (In Russ.)
https://doi.org/10.17116/jnevro2025125091124

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)
 
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Abstract:

OBJECTIVE

To identify informative predictors of the development and progression of multiple sclerosis (MS) based on polygenic analysis of associations of polymorphic variants in the IL1R1, IL10, IL12B, IL2, IL2RA, and IL7R genes.

MATERIAL AND METHODS

The study included 247 patients with MS and 1271 control subjects. Associations of development and progression of MS with polymorphic variants of the IL1R1, IL10, IL12B, IL2, IL2RA, IL7, and IL7R genes were analyzed. The combinations of allelic variants associated with the disease were searched using the APSampler software, and predictive models of the development and progression of MS were developed using multifactorial logistic regression with step-by-step inclusion of variables.

RESULTS

The increased probability of MS was associated with the IL1R1 rs2287047 (recessive model, OR=2.2, pFDR=0.022), IL7R rs1494558 polymorphic variants (log additive model, OR=1.49, pFDR=0.003), and IL2RA rs12722580 *I/D genotype (codominant model, OR=1.67, pFDR=0.03). Reduced MS risk was associated with IL10 rs1800872 (recessive model, OR=0.38, pFDR=0.044), IL7R rs10624573 (dominant model, OR=0.67, pFDR=0.022), IL7R rs6897932 variants (recessive model, OR=0.21, pFDR=0.008), and IL2RA rs12722580 * D/D genotype (codominant model, OR=0.78, pFDR=0.03). Combinations (IL7R rs1494558*T+IL7R rs6897932*T, IL1R1 rs2287047*C+IL12B rs3212227*C and IL7R rs1494558*T/C+IL12B rs3212227*A) with a synergistic effect were identified, and predictive models of MS development and progression risk with a sufficiently high prognostic value were created.

CONCLUSION

The results of the study emphasize the importance of polymorphic variants of IL7R, IL1R1, IL2RA, and IL10 in the genetic predisposition to MS. The obtained models require validation and can be supplemented with other predictors to improve accuracy; nevertheless, they demonstrate important pathogenetic patterns and directions for further study.

Keywords:

multiple sclerosis
interleukins
genetic polymorphism
association analysis
predictive model
predictive medicine

Authors:

Timasheva Ya.R.

Ufa Federal Research Centre of the Russian Academy of Sciences;
Bashkir State Medical University

Nasibullin T.R.

Ufa Federal Research Centre of the Russian Academy of Sciences

Tuktarova I.A.

Ufa Federal Research Centre of the Russian Academy of Sciences

Erdman V.V.

Ufa Federal Research Centre of the Russian Academy of Sciences

Vashenko V.I.

Ufa Federal Research Centre of the Russian Academy of Sciences

Galiullin T.R.

Bashkir State Medical University

Lyutov O.V.

Bashkir State Medical University

Bakhtiiarova K.Z.

Bashkir State Medical University

Received:

13.11.2024

Accepted:

10.01.2025

Close metadata

References:

  1. Azizi G, Van den Broek B, Ishikawa LLW, et al. IL-7Rα on CD4(+) T cells is required for their survival and the pathogenesis of experimental autoimmune encephalomyelitis. J Neuroinflammation. 2024;21(1):253.  https://doi.org/10.1186/s12974-024-03224-2
  2. Arbelaez CA, Glatigny S, Duhen R, et al. IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets Involved in Experimental Autoimmune Encephalomyelitis. J Immunol. 2015;195(5):1974-1983. https://doi.org/10.4049/jimmunol.1403135
  3. Peerlings D, Mimpen M, Damoiseaux J. The IL-2 — IL-2 receptor pathway: Key to understanding multiple sclerosis. J Transl Autoimmun. 2021;4:100123. https://doi.org/10.1016/j.jtauto.2021.100123
  4. Lin M, Park S, Hayden A, et al. Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review. Ann Hematol. 2017;96(8):1241-1251. https://doi.org/10.1007/s00277-017-2993-y
  5. Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol. 2015;15(5):283-294.  https://doi.org/10.1038/nri3823
  6. Luís JP, Simões CJV, Brito RMM. The Therapeutic Prospects of Targeting IL-1R1 for the Modulation of Neuroinflammation in Central Nervous System Disorders. Int J Mol Sci. 2022;23(3):1731. https://doi.org/10.3390/ijms23031731
  7. Lee Y, Awasthi A, Yosef N, et al. Induction and molecular signature of pathogenic TH17 cells. Nat Immunol. 2012;13(10):991-999.  https://doi.org/10.1038/ni.2416
  8. Burman J, Zjukovskaja C, Svenningsson A, et al. Cerebrospinal fluid cytokines after autologous haematopoietic stem cell transplantation and intrathecal rituximab treatment for multiple sclerosis. Brain Communications. 2023;5(1):fcad011. https://doi.org/10.1093/braincomms/fcad011
  9. Göbel K, Ruck T, Meuth SG. Cytokine signaling in multiple sclerosis: Lost in translation. Mult Scler. 2018;24(4):432-439.  https://doi.org/10.1177/1352458518763094
  10. Kleiter I, Ayzenberg I, Araki M, et al. Tocilizumab, MS, and NMOSD. Mult Scler. 2016;22(14):1891-1892. https://doi.org/10.1177/1352458516643395
  11. Gilio L, Buttari F, Pavone L, et al. Fatigue in Multiple Sclerosis Is Associated with Reduced Expression of Interleukin-10 and Worse Prospective Disease Activity. Biomedicines. 2022;10(9):2058. https://doi.org/10.3390/biomedicines10092058
  12. Mandolesi G, Centonze D, Furlan R, et al. Interleukin-10 contrasts inflammatory synaptopathy and central neurodegenerative damage in multiple sclerosis. Front Mol Neurosci. 2024;17.  https://doi.org/10.3389/fnmol.2024.1430080
  13. Gregory SG, Schmidt S, Seth P, et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet. 2007;39(9):1083-1091. https://doi.org/10.1038/ng2103
  14. Beecham AH, Patsopoulos NA, Xifara DK, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45(11):1353-1360. https://doi.org/10.1038/ng.2770
  15. Hafler DA, Compston A, Sawcer S, et al. Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. New England Journal of Medicine. 2007;357(9):851-862.  https://doi.org/10.1056/NEJMoa073493
  16. Sawcer S, Hellenthal G, Pirinen M, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214-219.  https://doi.org/10.1038/nature10251
  17. De Jager PL, Jia X, Wang J, et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet. 2009;41(7):776-782.  https://doi.org/10.1038/ng.401
  18. Patsopoulos NA, Baranzini SE, Santaniello A, et al. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019;365(6460):eaav7188. https://doi.org/10.1126/science.aav7188
  19. Bashinskaya VV, Kulakova OG, Kiselev IS, et al. GWAS-identified multiple sclerosis risk loci involved in immune response: validation In Russians. J Neuroimmunol. 2015;282:85-91.  https://doi.org/10.1016/j.jneuroim.2015.03.015
  20. Matesanz F, Fedetz M, Collado-Romero M, et al. Allelic expression and interleukin-2 polymorphisms in multiple sclerosis. J Neuroimmunol. 2001;119(1):101-105.  https://doi.org/10.1016/S0165-5728(01)00354-X
  21. Al-Naseri MAS, Ad’hiah AH, Salman ED. The association between multiple sclerosis and genetic variations of TGFβ1 and IL2 genes in Iraqi patients. Meta Gene. 2019;19:253-257.  https://doi.org/10.1016/j.mgene.2019.01.001
  22. Martinelli-Boneschi F, Esposito F, Brambilla P, et al. A genome-wide association study in progressive multiple sclerosis. Mult Scler. 2012;18(10):1384-1394. https://doi.org/10.1177/1352458512439118
  23. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173.  https://doi.org/10.1016/S1474-4422(17)30470-2
  24. Timasheva Y, Zaplakhova O, Nasibullin T, et al. Association between allelic variants of IL2, IL2RA, and IL7R genes and multiple sclerosis. Russ J Genet. 2019;55:487-494.  https://doi.org/10.1134/S1022795419030153
  25. Timasheva YR, Balkhiyarova ZR, Nasibullin TR, et al. Multilocus associations of inflammatory genes with the risk of type 1 diabetes. Gene. 2019;707:1-8.  https://doi.org/10.1016/j.gene.2019.04.085
  26. Timasheva Y, Nasibullin TR, Tuktarova IA, et al. Multilocus evaluation of genetic predictors of multiple sclerosis. Gene. 2022;809:146008. https://doi.org/10.1016/j.gene.2021.146008
  27. González JR, Armengol L, Solé X, et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics. 2007;23(5):654-655.  https://doi.org/10.1093/bioinformatics/btm025
  28. Favorov AV, Andreewski TV, Sudomoina MA, et al. A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans. Genetics. 2005;171(4):2113-2121. https://doi.org/10.1534/genetics.105.048090
  29. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Method. 1995;57:289-300.  https://doi.org/10.1111/j.2517-6161.1995.tb02031.x
  30. Cortina-Borja M, Smith AD, Combarros O, Lehmann DJ. The synergy factor: a statistic to measure interactions in complex diseases. BMC Res Notes. 2009;2:105.  https://doi.org/10.1186/1756-0500-2-105
  31. Winer H, Rodrigues GOL, Hixon JA, et al. IL-7: Comprehensive review. Cytokine. 2022;160:156049. https://doi.org/10.1016/j.cyto.2022.156049
  32. Lundström W, Highfill S, Walsh STR, et al. Soluble IL7Rα potentiates IL-7 bioactivity and promotes autoimmunity. PNAS. 2013;110(19):E1761-E1770. https://doi.org/10.1073/pnas.1222303110
  33. Kiselev I, Bashinskaya V, Baulina N, et al. Genetic differences between primary progressive and relapsing-remitting multiple sclerosis: The impact of immune-related genes variability. Mult Scler Relat Disord. 2019;29:130-136.  https://doi.org/10.1016/j.msard.2019.01.033
  34. Zhang R, Duan L, Jiang Y, et al. Association between the IL7R T244I polymorphism and multiple sclerosis: a meta-analysis. Mol Biol Rep. 2011;38(8):5079-5084. https://doi.org/10.1007/s11033-010-0654-5
  35. Wu S, Liu Q, Zhu JM, et al. Association between the IL7R T244I polymorphism and multiple sclerosis risk: a meta analysis. Neurol Sci. 2016;37(9):1467-1474. https://doi.org/10.1007/s10072-016-2608-8
  36. Lundtoft C, Seyfarth J, Jacobsen M. IL7RA genetic variants differentially affect IL-7Rα expression and alternative splicing: a role in autoimmune and infectious diseases? Genes Immun. 2020;21(2):83-90.  https://doi.org/10.1038/s41435-019-0091-y
  37. Pietzner M, Wheeler E, Carrasco-Zanini J, et al. Mapping the proteo-genomic convergence of human diseases. Science. 2021;374(6569):eabj1541. https://doi.org/10.1126/science.abj1541
  38. Yılmaz V, Yentür SP, Saruhan-Direskeneli G. IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine. 2005;30(4):188-194.  https://doi.org/10.1016/j.cyto.2005.01.006
  39. Nemati M, Ebrahimi H, Hajghani H, et al. Association of Interleukin-12B Gene Polymorphism With Multiple Sclerosis in Patients From Southeast of Iran. Arch Neurosci. 2018;5(2):e63360. https://doi.org/10.5812/archneurosci.63360
  40. Benešová Y, Vašků A, Bienertová-Vašků J. Association of interleukin 6, interleukin 7 receptor alpha, and interleukin 12B gene polymorphisms with multiple sclerosis. Acta Neurol Belg. 2018;118(3):493-501.  https://doi.org/10.1007/s13760-018-0994-9
  41. Miteva L, Trenova A, Slavov G, Stanilova S. IL12B gene polymorphisms have sex-specific effects in relapsing–remitting multiple sclerosis. Acta Neurol Belg. 2019;119(1):83-93.  https://doi.org/10.1007/s13760-018-01066-3
  42. Huang J, Yang Y, Zhou F, et al. Meta-analysis of the IL23R and IL12B polymorphisms in multiple sclerosis. Int J Neurosci. 2016;126(3):205-212.  https://doi.org/10.3109/00207454.2015.1007508
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