title: Relevance of IL7R genotype and mRNA expression in Dutch patients with multiple sclerosis.
abstract: BACKGROUND
  The interleukin 7 receptor (IL7R) has been recognized as a susceptibility gene for Multiple Sclerosis (MS). Analysis of rs6897932 (the most strongly MS-associated single nucleotide polymorphism (SNP)), showed effects of genotype on the relative expression of membrane-bound to total amount of IL7R mRNA.
  
  
  OBJECTIVE
  We assessed the relevance of IL7R on MS phenotype (including clinical and magnetic resonance imaging (MRI) parameters) at DNA and mRNA level in Dutch patients with MS.
  
  
  METHODS
  The genotype of rs6897932 was analyzed in 697 patients with MS and 174 healthy controls. The relevance of genotype and carriership of the C allele on MS phenotype (disease activity and severity, using clinical and MRI parameters) was assessed. In addition, relative gene expression of membrane-bound to total IL7R mRNA was analyzed with respect to disease phenotype in a subgroup of 95 patients with early relapsing MS.
  
  
  RESULTS
  In particular, homozygosity for the risk allele is a risk factor for MS in our population (OR(CC vs CT and TT) = 1.65 (95% CI: 1.18-2.30), two-sided p = 0.004). However, no effect of genotype or the relative expression of membrane-bound IL7R (presence of exon 6-7) to total amount of IL7R mRNA (presence of exon 4-5) was found on MS phenotype.
  
  
  CONCLUSIONS
  Homozygosity for the IL7R exon 6 rs6897932 C allele is associated with a higher risk for MS in our Dutch population. No effect was found of genotype or mRNA expression on disease phenotype.
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. m.sombekke@vumc.nl
authors.forename: M H
authors.initials: MH
authors.lastname: Sombekke
authors.forename: L F
authors.initials: LF
authors.lastname: van der Voort
authors.forename: J J
authors.initials: JJ
authors.lastname: Kragt
authors.forename: J M
authors.initials: JM
authors.lastname: Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Guzel
authors.forename: A
authors.initials: A
authors.lastname: Visser
authors.forename: C B M
authors.initials: CB
authors.lastname: Oudejans
authors.forename: J B A
authors.initials: JB
authors.lastname: Crusius
authors.forename: A Salvador
authors.initials: AS
authors.lastname: Peña
authors.forename: H
authors.initials: H
authors.lastname: Vrenken
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: J
authors.initials: J
authors.lastname: Killestein
mesh_terms: D000483:Alleles; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D009426:Netherlands; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis*; D020395:Receptors, Interleukin-7 / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D020395:Receptors, Interleukin-7