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

Multiple Sclerosis Center, Department of Neurology, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS ONE (Impact Factor: 3.23). 10/2013; 8(10):e75565. DOI: 10.1371/journal.pone.0075565
Source: PubMed


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.
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).
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.
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.

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Available from: Emmanuelle Waubant, Mar 07, 2014
    • "Most prior genetic association studies focus on MS susceptibility, rarely examining genetic influences on MS phenotype and initial symptoms . One recent study identified several known MS susceptibility genes that impact the early CNS attack location (Mowry et al., 2013). However, among analysed predictors of optic nerve involvement, only the CD6 polymorphism conferred reduced odds of ON as an attack location , and no significant associations with other polymorphisms were found. "
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