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Association of Il2ra and Multiple Sclerosis Risk: A Case Control, Systematic Review, and Meta-Analysis Study Publisher Pubmed



Rangani F1 ; Rakhshi N2 ; Kadkhoda Mezerji Z3 ; Alikhah A4 ; Dehghanzad R5 ; Abbasi B6 ; Ahmadi A7 ; Nikravesh A2 ; Pahlevan Kakhki M1
Authors
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Authors Affiliations
  1. 1. Department of Clinical Neuroscience, Karolinska Institutet, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, SE-171 76, Sweden
  2. 2. Department of Medical Biotechnology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
  3. 3. Department of Medical Biotechnology and Nanotechnology, Mashhad University of Medical Sciences, Mashhad, Iran
  4. 4. Department of Pathology and Laboratory Medicine, Schulich School of Medicine, University of Western Ontario, London, Canada
  5. 5. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Biology, Faculty of Basic Sciences, Zabol University, Zabol, Iran
  7. 7. Department of Biological Science and Technology, Faculty of Bio and Nano Science and Technology, Persian Gulf University, Bushehr, Iran

Source: Journal of the Neurological Sciences Published:2025


Abstract

The interleukin-2 receptor alpha chain (IL2RA) gene has been implicated in multiple sclerosis (MS) susceptibility, particularly through the rs2104286 and rs12722489 SNPs. However, previous studies have yielded inconsistent results across different populations, likely due to small sample sizes and ethnic variations. This study aimed to investigate the association of IL2RA SNPs with MS risk in eastern Iranian population and through a comprehensive meta-analysis. Our case-control study included 400 Iranian individuals from North Khorasan and Sistan & Baluchistan provinces, comprising 200 MS patients across all subtypes and genders and 200 controls. The meta-analysis incorporated pooled odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the strength of these associations. Our case-control findings demonstrated a significant association between rs2104286 and MS risk, which was further supported by the meta-analysis in Iranian populations. Specifically, the association was observed at both the genotype (P = 0.001) and allelic (P = 0.003) levels in North Khorasan and at the genotype level in Sistan & Baluchistan (P = 0.001). A global meta-analysis of rs2104286, encompassing 24,931 MS patients and 36,036 controls, revealed a significant association between the A allele and all genotype models with increased MS risk (P < 0.05). Similarly, a meta-analysis of rs12722489, including 19,797 MS patients and 32,085 controls, identified the CC + CT genotype as a risk factor for MS (P = 0.04). In conclusion, our findings suggest that the rs2104286 A allele and rs12722489 CC + CT genotype are associated with an increased risk of MS in both Caucasian and Asian populations, including Iranians. © 2025 The Author(s)
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