Interleukin 6 SNP rs1818879 Regulates Radiological and Inflammatory Activity in Multiple Sclerosis

Genes (Basel). 2022 May 17;13(5):897. doi: 10.3390/genes13050897.

Abstract

(1) Background: The clinical course of multiple sclerosis (MS) is critically influenced by the expression of different pro-inflammatory and anti-inflammatory cytokines. Interleukin 6 (IL-6) represents a major inflammatory molecule previously associated with exacerbated disease activity in relapsing remitting MS (RR-MS); however, the role of single-nucleotide polymorphisms (SNPs) in the IL-6 gene has not been fully elucidated in MS. (2) Methods: We explored in a cohort of 171 RR-MS patients, at the time of diagnosis, the associations between four IL-6 SNPs (rs1818879, rs1554606, rs1800797, and rs1474347), CSF inflammation, and clinical presentation. (3) Results: Using principal component analysis and logistic regression analysis we identified an association between rs1818879, radiological activity, and a set of cytokines, including the IL-1β, IL-9, IL-10, and IL-13. No significant associations were found between other SNPs and clinical or inflammatory parameters. (4) Conclusions: The association between the rs1818879 polymorphism and subclinical neuroinflammatory activity suggests that interindividual differences in the IL-6 gene might influence the immune activation profile in MS.

Keywords: CSF; Interleukin 6; SNPs; multiple sclerosis; neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / genetics
  • Humans
  • Interleukin-6 / genetics*
  • Multiple Sclerosis* / diagnostic imaging
  • Multiple Sclerosis* / genetics
  • Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting* / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Cytokines
  • IL6 protein, human
  • Interleukin-6

Grants and funding

The study was supported by: FISM grants (Fondazione Italiana Sclerosi Multipla-cod. 2019/S/1 to D.C. and F.R.R. and FISM-Fondazione Italiana Sclerosi Multipla-cod. 2020/R-Multi/018 and financed or cofinanced with the 5 per mille public funding to M.S.B. and F.R.R.); Progetto di Rete RCR-2020-23670067 to IRCCS Neuromed; Ricerca corrente to IRCCS San Raffaele Roma; Progetto Nuovi biomarker diagnostici e terapeutici delle malattie neurodegenerative to D.C.; private donation in memory of Chiara Sardi to D.C.; F.D.V. was supported by a research fellowship FISM (cod. 2020/BS/003) and financed and co-financed with the 5 per mille public funding.