Multiple Sclerosis Susceptibility Genes: Associations With Relapse Severity and Recovery

PLoS One. 2013 Oct 9;8(10):e75416. doi: 10.1371/journal.pone.0075416. eCollection 2013.

Abstract

Objective: Patients with early multiple sclerosis (MS) have stereotyped attack severity and recovery. We sought to determine if polymorphisms in MS susceptibility genes are associated with these attack features or with the risk of a second attack.

Methods: 503 white subjects evaluated within a year of MS onset were included in the study. The severity of and recovery from the first two attacks were determined based on published definitions. Seventeen MS susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each polymorphism was evaluated in multivariate ordinal models, adjusted for the other polymorphisms, for its association with attack severity and recovery. We also assessed if these polymorphisms were associated with increased risk of a second attack.

Results: The MPHOSPH9 polymorphism was associated with greater attack severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack severity. The CD6 polymorphism tended to be associated with increased odds of worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event within a year.

Conclusions: Some MS susceptibility polymorphisms may be associated with attack severity, recovery, or frequency. Further characterization of these genes may lead to a better understanding of MS pathogenesis and to a more individualized treatment approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Glypicans / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Male
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / pathology*
  • Phosphoproteins / genetics
  • Polymorphism, Single Nucleotide / genetics
  • RGS Proteins / genetics
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD6 antigen
  • GPC5 protein, human
  • Glypicans
  • HLA-DRB1 Chains
  • Phosphoproteins
  • RGS Proteins
  • RGS1 protein, human
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF1A protein, human

Grant support

This study was supported by a National Multiple Sclerosis Society research grant (www.nmss.org; RG-3692A; PI E. Waubant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.