title: Association of multiple sclerosis susceptibility variants and early attack location in the CNS.
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.
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Mowry
authors.forename: Robert F
authors.initials: RF
authors.lastname: Carey
authors.forename: Maria R
authors.initials: MR
authors.lastname: Blasco
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.forename: Pablo
authors.initials: P
authors.lastname: Villoslada
authors.forename: Irina
authors.initials: I
authors.lastname: Malikova
authors.forename: Elaine
authors.initials: E
authors.lastname: Roger
authors.forename: R Phillip
authors.initials: RP
authors.lastname: Kinkel
authors.forename: Jamie
authors.initials: J
authors.lastname: McDonald
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
mesh_terms: D000328:Adult; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology*; D009902:Optic Neuritis / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology