Association of Multiple Sclerosis Susceptibility Variants and Early Attack Location in the CNS

Ellen Mahar Mowry, Robert F. Carey, Maria R. Blasco, Jean Pelletier, Pierre Duquette, Pablo Villoslada, Irina Malikova, Elaine Roger, R. Phillip Kinkel, Jamie McDonald, Peter Bacchetti, Emmanuelle Waubant

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Abstract

Objective:The anatomic location of subsequent relapses in early multiple sclerosis (MS) appears to be predicted by the first attack location. We sought to determine if genetic polymorphisms associated with MS susceptibility are associated with attack location.Methods:17 genome-wide association study-identified MS susceptibility polymorphisms were genotyped in 503 white, non-Hispanic patients seen within a year of MS onset. Their association with the CNS location of the first two MS attacks was assessed in multivariate repeated measures analyses (generalized estimating equations with robust standard errors).Results:The IL12A polymorphism was independently associated with increased odds of attacks involving the spinal cord (OR = 1.52, 95% CI 1.11, 2.07, p = 0.009), as was the IRF8 polymorphism (OR = 2.40, 95% CI [1.04, 5.50], p = 0.040). The IL7R polymorphism was associated with reduced odds of attacks involving the brainstem/cerebellum (OR = 0.46, 95% CI 0.22, 0.97, p = 0.041), as were the TNFRSF1A and IL12A polymorphisms. The CD6 polymorphism conferred reduced odds of optic neuritis as an attack location (OR = 0.69, 95% CI [0.49, 0.97], p = 0.034). Several other genes showed trends for association with attack location.Conclusions:Some of the MS susceptibility genes may be associated with MS attack location. The IL12A polymorphism is of particular interest given that interferon beta therapy appears to influence IL12 levels. These findings may lead to improved understanding of MS pathogenesis and treatment.

Original languageEnglish (US)
Article numbere75565
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 10 2013

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mowry, E. M., Carey, R. F., Blasco, M. R., Pelletier, J., Duquette, P., Villoslada, P., Malikova, I., Roger, E., Kinkel, R. P., McDonald, J., Bacchetti, P., & Waubant, E. (2013). Association of Multiple Sclerosis Susceptibility Variants and Early Attack Location in the CNS. PLoS One, 8(10), [e75565]. https://doi.org/10.1371/journal.pone.0075565