title: CD46 in a Spanish cohort of multiple sclerosis patients: genetics, mRNA expression and response to interferon-beta treatment.
abstract: BACKGROUND
  In a prior study of our group we found an up-regulation of CD46 expression in a cohort of Spanish multiple sclerosis (MS) patients.
  
  
  OBJECTIVE
  To evaluate the potential role of CD46 in the response to interferon-beta treatment in MS patients through the analysis of five tagging single nucleotide polymorphisms (SNPs) and measurement of mRNA.
  
  
  METHODS
  A total of 406 MS patients and 513 control patients were analysed for five SNPs at the CD46 locus. Furthermore, 163 MS patients and 163 matched control patients were analysed by RT-PCR for the CD46 mRNA expression in three blood samples (basal, and at 6 and 12 months of interferon-beta treatment) collected in the course of a 1-year follow-up.
  
  
  RESULTS
  Two genotypes of rs2724385 polymorphism (AT and TT) could be markers of response to interferon-beta therapy in MS patients (p=0.007 and p=0.006, respectively). Furthermore, the frequency of interferon-beta responders was 44.4% (32/72) in MS patients with an increased CD46 mRNA expression, vs. 65.9% (60/91) in patients with a decreased CD46 mRNA expression (p=0.006).
  
  
  CONCLUSIONS
  The present study shows that CD46 could be associated with the response to interferon-beta therapy; however, the genetic results should be replicated in an independent cohort and further studies are needed to confirm the role of CD46.
authors.affiliation: Servicio de Neurología, Hospital Clínico San Carlos, Ciudad Universitaria, Madrid, Spain. ralvarezlafuente@yahoo.es
authors.forename: Roberto
authors.initials: R
authors.lastname: Alvarez-Lafuente
authors.forename: Fiona
authors.initials: F
authors.lastname: Blanco-Kelly
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia-Montojo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
authors.forename: Virginia
authors.initials: V
authors.lastname: De Las Heras
authors.forename: Maria Inmaculada
authors.initials: MI
authors.lastname: Dominguez-Mozo
authors.forename: Manuel
authors.initials: M
authors.lastname: Bartolome
authors.forename: Angel
authors.initials: A
authors.lastname: Garcia-Martinez
authors.forename: Emilio Gomez
authors.initials: EG
authors.lastname: De la Concha
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D051916:Membrane Cofactor Protein / Q000235:genetics*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D016017:Odds Ratio; D018579:Patient Selection; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: C497857:CD46 protein, human; D005819:Genetic Markers; D007155:Immunologic Factors; D051916:Membrane Cofactor Protein; D012333:RNA, Messenger; D016899:Interferon-beta