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<p><b>Objective.</b> To identify informative predictors of the development and progression of multiple sclerosis (MS) using polygenic association analysis of polymorphic variants in the <i>IL1R1</i>, <i>IL10</i>, <i>IL12B</i>, <i>IL2</i>, <i>IL2RA</i>, and <i>IL7R</i> genes. <b>Materials and methods.</b> Associations of polymorphic variants of the <i>IL1R1</i>, <i>IL10</i>, <i>IL12B</i>, <i>IL2</i>, <i>IL2RA</i>, <i>IL7</i>, and <i>IL7R</i> genes with the development and progression of MS were analyzed in a study group consisting of 247 patients with MS and 1271 controls. A search for combinations of allelic variants associated with the disease was run using the APSampler program; prognostic models of the development and progression of MS were constructed using a multivariate logistic regression method with stepwise inclusion of variables. <b>Results.</b> An increased probability of MS was associated with polymorphic variants <i>IL1R1</i> rs2287047 (recessive model, OR = 2.2, <i>p</i><sub>FDR</sub> = 0.022), <i>IL7R</i> rs1494558 (log-additive model, OR = 1.49, <i>p</i><sub>DR</sub> = 0.003) and the <i>IL2RA</i> rs12722580*I/D genotype (codominant model, OR = 1.67, <i>p</i><sub>FDR</sub> = 0.03). A reduced risk of MS was associated with the variants <i>IL10</i> rs1800872 (recessive model, OR = 0.38, <i>p</i><sub>FDR</sub> = 0.044), <i>IL7R</i> rs10624573 (dominant model, OR = 0.67, <i>p</i><sub>FDR</sub> = 0.022), and <i>IL7R</i> rs6897932 (recessive model, OR = 0.21, <i>p</i><sub>FDR</sub> = 0.008), as well as the genotype <i>IL2RA</i> rs12722580* D/D (codominant model, OR = 0.78, <i>p</i><sub>FDR</sub> = 0.03). The combinations (<i>IL7R</i> rs1494558*T + <i>L7R</i> rs6897932*T, <i>IL1R1</i> rs2287047*C + <i>IL12B</i> rs3212227*C, and <i>IL7R</i> rs1494558*T/C + <i>IL12B</i> rs3212227*A) with synergistic effects were identified and predictive models of the risk of the development and progression of MS with sufficiently high prognostic significance were created. <b>Conclusions.</b> The results of this study emphasize the importance of polymorphic variants of <i>IL7R</i>, <i>IL1R1</i>, <i>IL2RA</i>, and <i>IL10</i> in the formation of hereditary predisposition to MS. These models require validation and can be supplemented with other predictors to improve accuracy, though they demonstrate important pathogenetic patterns and directions for further study.</p>

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Search for Informative Predictors of the Development and Progression of Multiple Sclerosis

  • 期刊论文

  • 发表日期：

    2026年3月20日

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  • Y. R. Timasheva,
  • T. R. Nasibullin,
  • I. A. Tuktarova,
  • V. V. Erdman,
  • V. I. Vashenko,
  • T. R. Galiullin,
  • O. V. Lyutov,
  • K. Z. Bakhtiyarova

摘要

Objective. To identify informative predictors of the development and progression of multiple sclerosis (MS) using polygenic association analysis of polymorphic variants in the IL1R1, IL10, IL12B, IL2, IL2RA, and IL7R genes. Materials and methods. Associations of polymorphic variants of the IL1R1, IL10, IL12B, IL2, IL2RA, IL7, and IL7R genes with the development and progression of MS were analyzed in a study group consisting of 247 patients with MS and 1271 controls. A search for combinations of allelic variants associated with the disease was run using the APSampler program; prognostic models of the development and progression of MS were constructed using a multivariate logistic regression method with stepwise inclusion of variables. Results. An increased probability of MS was associated with polymorphic variants IL1R1 rs2287047 (recessive model, OR = 2.2, pFDR = 0.022), IL7R rs1494558 (log-additive model, OR = 1.49, pDR = 0.003) and the IL2RA rs12722580*I/D genotype (codominant model, OR = 1.67, pFDR = 0.03). A reduced risk of MS was associated with the variants IL10 rs1800872 (recessive model, OR = 0.38, pFDR = 0.044), IL7R rs10624573 (dominant model, OR = 0.67, pFDR = 0.022), and IL7R rs6897932 (recessive model, OR = 0.21, pFDR = 0.008), as well as the genotype IL2RA rs12722580* D/D (codominant model, OR = 0.78, pFDR = 0.03). The combinations (IL7R rs1494558*T + L7R rs6897932*T, IL1R1 rs2287047*C + IL12B rs3212227*C, and IL7R rs1494558*T/C + IL12B rs3212227*A) with synergistic effects were identified and predictive models of the risk of the development and progression of MS with sufficiently high prognostic significance were created. Conclusions. The results of this study emphasize the importance of polymorphic variants of IL7R, IL1R1, IL2RA, and IL10 in the formation of hereditary predisposition to MS. These models require validation and can be supplemented with other predictors to improve accuracy, though they demonstrate important pathogenetic patterns and directions for further study.