title: Methylation of class II transactivator gene promoter IV is not associated with susceptibility to multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology.
  
  
  METHODS
  In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR.
  
  
  RESULTS
  No methylation or sequence variation of the MHC2TA promoter pIV was found.
  
  
  CONCLUSIONS
  The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK. sramagopalan@gmail.com
authors.forename: Sreeram V
authors.initials: SV
authors.lastname: Ramagopalan
authors.forename: David A
authors.initials: DA
authors.lastname: Dyment
authors.forename: Katie M
authors.initials: KM
authors.lastname: Morrison
authors.forename: Blanca M
authors.initials: BM
authors.lastname: Herrera
authors.forename: Gabriele C
authors.initials: GC
authors.lastname: Deluca
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lincoln
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Orton
authors.forename: Lahiru
authors.initials: L
authors.lastname: Handunnetthi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chao
authors.forename: A Dessa
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: George C
authors.initials: GC
authors.lastname: Ebers
mesh_terms: D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D004200:Diseases in Twins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014430:Twins, Monozygotic
chemical_list: D015534:Trans-Activators