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Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

Validation of IRF5 as multiple sclerosis risk gene: putative role in interferon beta therapy and human herpes virus-6

K Vandenbroeck1, I Alloza, B Swaminathan

  • 1Neurogenomiks, University of the Basque Country (UPV/EHU), Leioa, Spain.

Genes and Immunity
|September 24, 2010
PubMed

Insights

Interferon regulatory factor 5 (IRF5) gene polymorphisms are linked to multiple sclerosis (MS) susceptibility. These IRF5 variants may also influence human herpes virus-6 infection and response to interferon-beta therapy in MS patients.

Area of Science:

  • Immunogenetics
  • Neuroimmunology
  • Viral Immunology

Background:

  • Interferon regulatory factor 5 (IRF5) polymorphisms have been associated with multiple sclerosis (MS) susceptibility.
  • Irf5-deficient mice show increased susceptibility to viral infections due to impaired type I interferon (IFN) induction.

Purpose of the Study:

  • To investigate the association of two specific IRF5 polymorphisms (rs4728142 and rs3807306) with MS predisposition.
  • To determine if these polymorphisms correlate with human herpes virus-6 (HHV-6) replication or response to interferon-beta (IFN-β) therapy in MS patients.

Main Methods:

  • Genotyping of 1494 MS patients and 1506 controls for IRF5 polymorphisms rs4728142 and rs3807306 using TaqMan assays.
  • Classification of 106 patients as IFN-β responders and 112 as non-responders based on clinical outcomes over a 2-year follow-up.
  • Statistical analysis including Mantel-Haenszel odds ratio calculation.

Main Results:

  • Combined analysis showed a significant association between IRF5 polymorphisms rs4728142 and rs3807306 and MS susceptibility (OR=1.14, P<0.002).
  • Trends suggested an association between the rs3807306T variant and HHV-6 infection (P=0.05) and IFN-β therapy response (P=0.09).

Conclusions:

  • IRF5 polymorphisms rs4728142 and rs3807306 are associated with multiple sclerosis susceptibility.
  • Further research is warranted to explore the role of IRF5 variants in HHV-6 infection and IFN-β treatment response in MS.

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